Biosublime.com/LSD, Birth & TraumaThe Biological Role of the
Endogenous Hallucinogens
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Part 1 LSD Birth Memory
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PART 1. THE IMPRINT, ITS RECALL, ITS DISSIPATION AND ITS BIOLOGICAL MECHANISM
1.1 PROCEDURE
Notes from the evening and next day after the session.
In this initial session the LSD dose was known only qualitatively as a low dose by street standards in the 1970s. A small 4mm blotter square containing approximately 100ug (micrograms) of the drug was divided into four sections with a razor blade cutting from corner to corner. The assumed dose of 25ug was based on the reckless assumption that the alleged 100ug was distributed evenly within the blotter material. The authenticity of LSD was verified to some extent by accounts of more classical LSD experiences from other individuals self-experimenting with this particular lot of “street drug” in the mid ‘70s. This dose was taken using oral mastication and water by an 85kg naïve male subject (here, named M) in his mid 40s in a restful, attractive and safe atmosphere under the care of a man and wife alert to any needs that might arise. Aside from occasional checking, the subject was left alone. The session was carefully recorded in a logbook the next day.
1.2 Results
The six to seven hour session was dominated by intense sensations of palate pressure and skull shearing forces. However, before this, about a half hour after ingestion, M experienced feelings of “healing”, calm relaxation, pleasurable anticipation and increased intestinal activity. There was a short interval of watching an amusing dreamlike movie, in which two seemingly spiritual avatars dressed in red pantaloons were fighting with curved swords with the jerky movements seen in Indonesian shadow movies, presumably over M’s soul. This was followed by a comfortable feeling of dulled, pleasurable body sensations, relaxed gazing and the desire to remain motionless, best characterized as the “stoned” state of narcosis.
1.2.1 Skull Sensations
Within the next hour, intense feelings of pressure began with the palate. Soon, strong sensations proceeded from the palate upward into the bony area above the upper teeth, then across the bridge of the nose and into the forehead. These sensations were not superficial, but felt deep in the bone.
As shown in Figure 1, the sequence was divided into specific locations in the head, each sensation having its own time frame: First, the palate (the palatine process of the maxilla, not the palatine bone), then, the bone holding the upper teeth (the maxilla), the nasal bone and finally, the forehead (frontal squama of the frontal bone). These sensations traversing from the palate upwards along the front of the skull continued to repeat in the same order, but eventually, only the palate and maxilla sensations were felt. The earlier forehead sensations were felt as a line of shearing, the left and the right side forced in opposite directions. This sequence of pressure and shearing was alarming, but not painful, perhaps as it took place within the overall sensation of narcosis and anesthesia that began earlier.
1.2.2 FLASHBACKS
With small dose of LSD, a very old memory was sent into conscious awareness. Its retrieval repeated itself spontaneously over a period of some weeks in diminishing intensity until it no longer appeared. These apparent "flashbacks" returned in mid to late afternoon, but mostly a short time after the subject awakened from sleep in the morning. After weakening for some weeks they disappeared entirely. The subject formed the distinct sense that LSD initiated a process that continued naturally on its own until the source of these sensations had somehow been exhausted. The skull sensations never returned in subsequent LSD trials, regardless of dose.
1.3 THE PHENOMENON IDENTIFIED
Several weeks after this session, it was learned that these palate and skull sensations followed, unmistakably, what the baby would feel while undergoing a practice of birthing fashionable in the 1930s (M was born in 1932) (Grof S. ca 1975). In this obstetric protocol, the mother was given a mixture of morphine and scopolamine to promote anesthesia, sleep and amnesia. Because this “twilight sleep” protocol would diminish the contractions, the baby, now incapacitated under the influence of these drugs in the placental blood, is worked out of the birth canal by he roof of its mouth with the first two fingers of the doctor’s hand. Vestiges of this procedure are still applied to turn the baby’s head through the birth canal. Until this explanation by Dr. Grof, neither the M nor the observers involved had any inkling of the meaning of these skull sensations, putting to rest the question of hallucinogen suggestibility. After Dr. Grof’s suggestion, M recalled (as the last of three children) being told as a teenager by his mother that his was the easiest; she learned of the birth only after she awoke.
1.4 GENERAL DISCUSSION
The fact that this first LSD encounter was remarkable had as much to do with learning about its connection with birthing protocols in the 1930s as with the pristine physical simplicity of the experience. With this information, physical sensations of skull pressure and anesthesia could be interpreted stepwise as a memory trace planted decades ago by specific features of a certain obstetric protocol. Clearly, the sequential release of sensory memory for specific parts of the skull was a recapitulation of events experienced in much the same sequence they would have occurred during the birth process. Apparently, LSD opened a memory location hidden somewhere in the brain and released its impulses into the cerebral sensory cortices that specialize in interpreting these in conscious awareness.
A well-documented system of this kind exists in the brainstem. The spontaneous firing of serotonergic (5-HT) neurons within the raphe nuclei of the brainstem chronically suppresses the activity of other nuclei within the reticular formation (RF). RF is a vertical twig of complex connections within the brainstem that has many functions, including control of the sleep-awake cycle, respiration and body temperature. The hypothetical model is based on the following: As long as these raphe neurons are actively firing, a reticular nucleus (RN) within RF is inactive and impulse traffic to and from the memory substrate is blocked. Thus, the shutting down of raphe firing by LSD or similar serotonergic agonist activates RN to unblock the flow of these sensory memory impulses from memory storage to the cerebral cortices that specialize in conscious awareness of these as feeling. This process is bi-directional: As seen with the fetus at birth, sensory impulses from the outside world are consolidated into this memory during the same suppression of Ra and dis-inhibition of RN. This mechanism is referred to as the RaRN model.
A serotonergic agonist isn't the only way to stop the firing of raphe 5-HT neurons. The habenula, intimately associated with the pineal gland, can shut off Ra firing as well through direct Ra enervation to alter saccadic eye movement. ( ). Habenular involvement is deferred for later arguments on REM sleep, owing to the assumption that fetal and adult neural conditions both involve the hallucinogen within the context of birth.
Basically, what follows is a survey of established pharmacology of hallucinogens and scopolamine to determine if an examination of these effects in terms of the RaRN model can reveal insights into birth, trauma and present views of hallucinogenic drugs. It will be argued that scopolamine’s inhibition of the hypothalamus at birth accounts for the long dormancy of a traumatic memory released decades later by LSD and may be an additional requirement within the RaRN model, thus reducing it’s application generally. This analysis begins with some documentation relevant to the RaRN idea and is followed by a brief history of the engram and a discussion of flashbacks and trauma within the context of Twilight sleep and scopolamine.
1.1 PROCEDURE
Notes from the evening and next day after the session.
In this initial session the LSD dose was known only qualitatively as a low dose by street standards in the 1970s. A small 4mm blotter square containing approximately 100ug (micrograms) of the drug was divided into four sections with a razor blade cutting from corner to corner. The assumed dose of 25ug was based on the reckless assumption that the alleged 100ug was distributed evenly within the blotter material. The authenticity of LSD was verified to some extent by accounts of more classical LSD experiences from other individuals self-experimenting with this particular lot of “street drug” in the mid ‘70s. This dose was taken using oral mastication and water by an 85kg naïve male subject (here, named M) in his mid 40s in a restful, attractive and safe atmosphere under the care of a man and wife alert to any needs that might arise. Aside from occasional checking, the subject was left alone. The session was carefully recorded in a logbook the next day.
1.2 Results
The six to seven hour session was dominated by intense sensations of palate pressure and skull shearing forces. However, before this, about a half hour after ingestion, M experienced feelings of “healing”, calm relaxation, pleasurable anticipation and increased intestinal activity. There was a short interval of watching an amusing dreamlike movie, in which two seemingly spiritual avatars dressed in red pantaloons were fighting with curved swords with the jerky movements seen in Indonesian shadow movies, presumably over M’s soul. This was followed by a comfortable feeling of dulled, pleasurable body sensations, relaxed gazing and the desire to remain motionless, best characterized as the “stoned” state of narcosis.
1.2.1 Skull Sensations
Within the next hour, intense feelings of pressure began with the palate. Soon, strong sensations proceeded from the palate upward into the bony area above the upper teeth, then across the bridge of the nose and into the forehead. These sensations were not superficial, but felt deep in the bone.
As shown in Figure 1, the sequence was divided into specific locations in the head, each sensation having its own time frame: First, the palate (the palatine process of the maxilla, not the palatine bone), then, the bone holding the upper teeth (the maxilla), the nasal bone and finally, the forehead (frontal squama of the frontal bone). These sensations traversing from the palate upwards along the front of the skull continued to repeat in the same order, but eventually, only the palate and maxilla sensations were felt. The earlier forehead sensations were felt as a line of shearing, the left and the right side forced in opposite directions. This sequence of pressure and shearing was alarming, but not painful, perhaps as it took place within the overall sensation of narcosis and anesthesia that began earlier. 1.2.2 FLASHBACKS
With small dose of LSD, a very old memory was sent into conscious awareness. Its retrieval repeated itself spontaneously over a period of some weeks in diminishing intensity until it no longer appeared. These apparent "flashbacks" returned in mid to late afternoon, but mostly a short time after the subject awakened from sleep in the morning. After weakening for some weeks they disappeared entirely. The subject formed the distinct sense that LSD initiated a process that continued naturally on its own until the source of these sensations had somehow been exhausted. The skull sensations never returned in subsequent LSD trials, regardless of dose.
1.3 THE PHENOMENON IDENTIFIED
Several weeks after this session, it was learned that these palate and skull sensations followed, unmistakably, what the baby would feel while undergoing a practice of birthing fashionable in the 1930s (M was born in 1932) (Grof S. ca 1975). In this obstetric protocol, the mother was given a mixture of morphine and scopolamine to promote anesthesia, sleep and amnesia. Because this “twilight sleep” protocol would diminish the contractions, the baby, now incapacitated under the influence of these drugs in the placental blood, is worked out of the birth canal by he roof of its mouth with the first two fingers of the doctor’s hand. Vestiges of this procedure are still applied to turn the baby’s head through the birth canal. Until this explanation by Dr. Grof, neither the M nor the observers involved had any inkling of the meaning of these skull sensations, putting to rest the question of hallucinogen suggestibility. After Dr. Grof’s suggestion, M recalled (as the last of three children) being told as a teenager by his mother that his was the easiest; she learned of the birth only after she awoke.
1.4 GENERAL DISCUSSION
The fact that this first LSD encounter was remarkable had as much to do with learning about its connection with birthing protocols in the 1930s as with the pristine physical simplicity of the experience. With this information, physical sensations of skull pressure and anesthesia could be interpreted stepwise as a memory trace planted decades ago by specific features of a certain obstetric protocol. Clearly, the sequential release of sensory memory for specific parts of the skull was a recapitulation of events experienced in much the same sequence they would have occurred during the birth process. Apparently, LSD opened a memory location hidden somewhere in the brain and released its impulses into the cerebral sensory cortices that specialize in interpreting these in conscious awareness.
A well-documented system of this kind exists in the brainstem. The spontaneous firing of serotonergic (5-HT) neurons within the raphe nuclei of the brainstem chronically suppresses the activity of other nuclei within the reticular formation (RF). RF is a vertical twig of complex connections within the brainstem that has many functions, including control of the sleep-awake cycle, respiration and body temperature. The hypothetical model is based on the following: As long as these raphe neurons are actively firing, a reticular nucleus (RN) within RF is inactive and impulse traffic to and from the memory substrate is blocked. Thus, the shutting down of raphe firing by LSD or similar serotonergic agonist activates RN to unblock the flow of these sensory memory impulses from memory storage to the cerebral cortices that specialize in conscious awareness of these as feeling. This process is bi-directional: As seen with the fetus at birth, sensory impulses from the outside world are consolidated into this memory during the same suppression of Ra and dis-inhibition of RN. This mechanism is referred to as the RaRN model.
A serotonergic agonist isn't the only way to stop the firing of raphe 5-HT neurons. The habenula, intimately associated with the pineal gland, can shut off Ra firing as well through direct Ra enervation to alter saccadic eye movement. ( ). Habenular involvement is deferred for later arguments on REM sleep, owing to the assumption that fetal and adult neural conditions both involve the hallucinogen within the context of birth.
Basically, what follows is a survey of established pharmacology of hallucinogens and scopolamine to determine if an examination of these effects in terms of the RaRN model can reveal insights into birth, trauma and present views of hallucinogenic drugs. It will be argued that scopolamine’s inhibition of the hypothalamus at birth accounts for the long dormancy of a traumatic memory released decades later by LSD and may be an additional requirement within the RaRN model, thus reducing it’s application generally. This analysis begins with some documentation relevant to the RaRN idea and is followed by a brief history of the engram and a discussion of flashbacks and trauma within the context of Twilight sleep and scopolamine.
1.4.1 THE HALLUCINOGEN-RAPHE-RETICULAR MODEL (RaRN)
The raphe nuclei are parts of the brainstem reticular formation (RF), a complex net of connections and over 100 nuclei, whose functional descriptions are diverse and still remain incomplete. These nuclei include the so-called reticular nuclei (RN), having diffuse boundaries within the RF (Nolte, 2001). As intimate parts of RF, these RN are assumed here to be under the same control by raphe activity. The basic idea is illustrated crudely in Figure 2.
Pictures of RF and the raphe nuclei in the brainstem are shown later in Figures 4 and 4a. The anatomical identity and location of specific Ra and RN will be presented in later sections.
A cautionary note: Arguments made throughout are intended to account for M’s skull incident in terms of this RaRN model, itself derived from the incident. One problem is that M is human, while most of the supporting data for the model is derived from research on non-humans, notably the rat. Some interesting species differences are found between rats and primates and these will be discussed. This has to do with the kinds of experimentation showing the preferences LSD has for receptors in the animals vis-à-vis humans, the latter not accessible to similar experimentation, at least not legally. Nevertheless, the discussion will forge ahead with the assumption that the raphe receptor recognized by LSD (the 5-HT1a) is the same in humans and the rat with respect to location and raphe function.
It is well known that raphe and locus ceruleus nuclei inhibit the closely associated reticular formation (RF) of the reticular activating system within the brainstem when they are in the active state, firing continuously and spontaneously (cf Cabot and Wild, 1975; Hobson et al, 1979; Trulson and Jacobs, 1996). Thus, the model: Normally, a brainstem reticular (RN) blocks impulse flow from a memory site to the cerebral cortical areas that specialize in conscious awareness. This blockage arises from the chronic inhibitory activity of a raphe (Ra) nucleus that controls RN. The raphe nuclei maintain this inhibition by spontaneous firing of serotonergic neurons (specific for serotonin), driven by autoreceptors within their post-synaptic dendrite membranes (Nichols, 2004). This inhibition would account for the decades-long storage of M’s physical memory within some storage nucleus that is blocked by a reticular nucleus to be identified below. Because the autorecptor gets it's neurotransmitter (serotonin) from its own neuron, this chronic firing of the raphe 5HT neurons would be maintained in the presence of monoamine oxidase (a)(MAO a), which would degrade circulating monoamines such as LSD or EH (Aghajanian et al, 1979). The well-established suppression of raphe activity by sufficient amounts of LSD then accounts for the release of memory into M’s conscious awareness (Aghaganian et al, 1968, 1972, Aghajanian and Haigler, 1975). By assuming that this neural condition of RN activation with the adult on LSD is the same as that of the fetus during birth, it follows that the nature of this process is reciprocal: the original sensory impulses were stored at birth by the same process of raphe inhibition in response to an endogenous hallucinogen, i.e., the RaRN model provides reversibility for storing and retrieving a hidden memory.
1.4.2 ENGRAMS, IMPRINTS AND MEMORY TRACES—Primitive and Subcortical
M’s first LSD experience could be a prime example of the engram, a term used by neurophysiologists and popularized by the Scientologists. To a neuropsychologist, an engram is defined as a hypothetical process producing a memory trace lodged somewhere in the unconscious to affect some central nervous system process by some unknown, unconscious process. The word, “engram” was borrowed by the scientologists to define a buried memory having unconscious adverse influence on mental and physical behavior to be monitored by skin conductivity and “cleared” by various associations. To the early 20th century biologist Richard Wolfgang Semon (1859-1918) it was a mneme, from the ancient Greek Muse of memory, Mnemosyne or Mneme, (as in mnemonic) representing much the same thing (Semon, 1921). This concept was adopted by behaviorists and extended to the idea of the “meme” as a cultural unit (Dawkins, 1976). “Imprint”, might be a another name for this kind of phenomenon, since the character of M’s LSD experience, like that of experimental animals, is argued below to be sub-cortical. The word “imprint” might better suggest the nature of this memory as encoded and non-verbal recognition of associations. The LSD recall to be described clearly conforms to these definitions of an engram, imprint or memory trace, where LSD unlocked some “storage area” within the brain and allowed impulses from this memory to flow—once again--- into thalamic and cerebral cortical areas that specialize in interpreting them as conscious awareness.
A well known example of imprinting is seen in the behavior of young geese, as they lock onto and follow the first image they see, whether it is a mother goose or a human being in a motorized hang-glider. For them, as will be argued for the fetus, it is a critical time, in which they are in a condition to receive and store the image. Beyond this time, the image is locked away in some memory crypt and their impulse to follow any figure other than the initial image is gone. Importantly, this line of research extended into Pavlovian experiments on rabbit eye-blink/sound association by Thompson and coworkers, and discussed as the scientific precedent for the “ON-OFF” nucleus analogous to the properties to be postulated here for a reticular/cerebellar nucleus interaction (Thompson and Krupa 1994). This little history is included to introduce the conclusions that 1) M’s memory is primitive and stored sub-cortically, probably in the cerebellum and 2) the concept of open/closed windows of developmental opportunity will be exemplified (Part 2).
1.4.3 On Flashbacks
The “flashbacks” testify to LSD as a mere trigger in a long process far outlasting the presence of the drug in the subject’s body. LSD may have been degraded by monoamine oxidase even before the sensations were completed during the session (see for example, Trulson and Jacobs, 1996). Presumably, the spontaneous occurrence of flashbacks at certain periods of the day reflects the same changes in the blocking nucleus to allow conscious recall of the same memory with such precision. It follows that an endogenous hallucinogen (EH) or an agent with similar molecular structure as LSD recognized the same receptor to inhibit raphe activity at the time of the flashback. On the other hand, another well-known inhibitory system could shut down raphe activity, which involves the neurotransmitter, gamma aminobutyric acid (GABA). This GABAergic system is widespread, it exists within raphe nuclei and is involved in raphe suppression (cf Nitz and Siegel, 1997). However, the issue of serotonergic inhibition by a psychoactive amine hasn’t been considered in this and many similar studies. While the GABAergic system may well be involved, it is the striking similarity of flashbacks to skull recall in the LSD session that favors the hallucinogen. It must involve a process so specific that it would require an LSD-like mechanism. The action of LSD to shut down the 5-HT raphe neurons has been shown to occur with both the direct and systemic application of LSD (Aghajanian, 1972).
The eventual disappearance of M’s flashbacks seen here raises the question about the generally pejorative view that pervades the literature (see Nichols, 2004). Flashbacks have a long negative reputation and have been associated with hallucinogen persisting perception disorder, “HPPD”-- to emphasize their character as the late appearance of “toxic” symptoms of LSD “injury” (Halpern and Pope, 2003; see Nichols, 2004 p. 135). On the other hand, flashbacks are distinguished from HPPD by others and defined as gentler echoes of the first hallucinogenic experience (Dart RC, et al eds, 2003). This view more clearly represents the flashback’s properties in M’s experience.
In contemplating why most flashback experiences with hallucinogens can be persistent, one issue stands out: The flashbacks experienced by M are subcortical in origin, as the fetus, like the mother, has no cerebrocortical memory of the birth, owing to the strong anti-cholinergic action of scopolamine on the cholinergic hippocampus and hypothalamus. Persistent flashbacks in the form of PTSD or post hallucinogenic exposure would include the adaptive efforts of the cerebral cortex to minimize the effects of fear and emotion originating from the amygdala-hippocampus axis. Obviously, the activation of the amygdala as part of the emerging memory would obscure the experience of flashbacks as signs of healing. M's mind was free of this cerebral influence.
A purely subcortical return and disappearance long after the initial LSD session could be interpreted more easily as symptoms of a healing process for erasing the memory in response to re-activating it. If it can be assumed that the activation of a toxic memory by LSD leads to a longer process of its dissolution, then the occurrence of disturbing flashbacks lasting years can be viewed as a prolonged, but unsuccessful, healing process to be expected for those not born by Twilight Sleep. The perceptual problem with this is that severe cases of flashbacks, i.e., HPPD, are disturbingly persistent over time to give the impression of permanent hallucinogenic injury. Since flashbacks and HPPD are phenomena that follow the initial hallucinogenic experience they will be viewed here as originating from the same healing process, the latter being incomplete. Moreover, posttraumatic stress disorder (PTSD) seen in severely traumatized individuals (Van der Kolk, 2006) will be included in this to comprise a trio of phenomena heralding the attempt by the organism to eliminate noxious memory. As illustrated by the properties of the RaRN mechanism, flashbacks, HPPD and PTSD are essentially the same, the latter two arising from incomplete resolution of the trauma. The persistence of the latter is accounted for by the properties of the RaRN model.
The RaRN model provides an answer to the persistence of HPPD and PTSD, since it is merely a means for opening and closing memory substrates under specific perceptual conditions. During the time of the flashback, a memory substrate is opened in response to raphe inhibition by DMT+. At this time this substrate is ready to receive additional sensory information that could reinforce the memory with new sensory input. The renewed perception of cerebral noxious symptoms attending the flashback would add to the burden of traumatic memory. For example, flashbacks are much more severe in recreational use of hallucinogens, as compared to their clinical use in therapy (Nichols, 2004). Obviously, the chaos resulting from the alarm of others would add to the open cerebral noxious contents in a recreational environment. The calmer and healing ambience of the therapeutic context would lessen the sensory influence. Indeed, in the RaRN model, the accumulation of sensory information by the open memory substrate would be additive such that new input during a flashback might add to, neutralize or displace the old. This possibility, intrinsic to the RaRN model, would account for the recent success in the treatment of PTSD with the ecstasy drug, MDMA (/www.maps.org/sys/nq.pl?id=1764&fmt=page). (Twenty out of twenty human PTSD subjects improved significantly). MDMA binds to hallucinogen receptors (Sprouse et al, 1989) and, as with LSD, would open the RaRN memory substrate to MDMA’s celebrated positive effects as new input in opposition to the noxious content of the memory. if the reinforcement was noxious, the resuming of RN blockage with the return of Ra activity would encase this new information along with the original to reinforce the trauma and lower the sensory threshold for triggering new flashbacks.
This facilitation of flashbacks in more draconian examples of trauma has been observed and explained by a model of synaptic plasticity that is hypothesized to establish “states” associated with PTSD (Perry et al, 1991). Also, this phenomenon of additional consolidation is well known in the model for treatment of PTSD with propranolol. In this case propranolol prevents additional hippocampal memory burden resulting from acetylcholine secreted by the excited amygdala. The comparison of these results with the RaRN model will be encountered in the next discussion of trauma within the subject of Twilight sleep. At this point, a similarity appears between M’s flashbacks and those flashbacks shown by clinicians to be common to posttraumatic stress disorder, PTSD. M’s flashbacks can be viewed as an experimental model that excludes the complication of cholinergic function within the hippocampus and the hypothalamus (below). It would represent an uncluttered experimental approach for the following reason: The flashbacks of severe trauma in those with PTSD may actually reflect an autonomous attempt by the organism to heal the trauma by opening the memory substrate and erase it as in M’s case -- but achieving only its reinforcement, owing to reconsolidation according to the RaRN model. With scopolamine, this reconsolidation might be avoided.
Lastly, the case for the nightly healing function of REM Sleep will be made on the basis of the flashbacks seen here as spontaneously occurring encores of the original memory recall, which disappear, never to return. Arguments are presented in this website on the page, REM Sleep Healing.
The raphe nuclei are parts of the brainstem reticular formation (RF), a complex net of connections and over 100 nuclei, whose functional descriptions are diverse and still remain incomplete. These nuclei include the so-called reticular nuclei (RN), having diffuse boundaries within the RF (Nolte, 2001). As intimate parts of RF, these RN are assumed here to be under the same control by raphe activity. The basic idea is illustrated crudely in Figure 2.
Pictures of RF and the raphe nuclei in the brainstem are shown later in Figures 4 and 4a. The anatomical identity and location of specific Ra and RN will be presented in later sections.A cautionary note: Arguments made throughout are intended to account for M’s skull incident in terms of this RaRN model, itself derived from the incident. One problem is that M is human, while most of the supporting data for the model is derived from research on non-humans, notably the rat. Some interesting species differences are found between rats and primates and these will be discussed. This has to do with the kinds of experimentation showing the preferences LSD has for receptors in the animals vis-à-vis humans, the latter not accessible to similar experimentation, at least not legally. Nevertheless, the discussion will forge ahead with the assumption that the raphe receptor recognized by LSD (the 5-HT1a) is the same in humans and the rat with respect to location and raphe function.
It is well known that raphe and locus ceruleus nuclei inhibit the closely associated reticular formation (RF) of the reticular activating system within the brainstem when they are in the active state, firing continuously and spontaneously (cf Cabot and Wild, 1975; Hobson et al, 1979; Trulson and Jacobs, 1996). Thus, the model: Normally, a brainstem reticular (RN) blocks impulse flow from a memory site to the cerebral cortical areas that specialize in conscious awareness. This blockage arises from the chronic inhibitory activity of a raphe (Ra) nucleus that controls RN. The raphe nuclei maintain this inhibition by spontaneous firing of serotonergic neurons (specific for serotonin), driven by autoreceptors within their post-synaptic dendrite membranes (Nichols, 2004). This inhibition would account for the decades-long storage of M’s physical memory within some storage nucleus that is blocked by a reticular nucleus to be identified below. Because the autorecptor gets it's neurotransmitter (serotonin) from its own neuron, this chronic firing of the raphe 5HT neurons would be maintained in the presence of monoamine oxidase (a)(MAO a), which would degrade circulating monoamines such as LSD or EH (Aghajanian et al, 1979). The well-established suppression of raphe activity by sufficient amounts of LSD then accounts for the release of memory into M’s conscious awareness (Aghaganian et al, 1968, 1972, Aghajanian and Haigler, 1975). By assuming that this neural condition of RN activation with the adult on LSD is the same as that of the fetus during birth, it follows that the nature of this process is reciprocal: the original sensory impulses were stored at birth by the same process of raphe inhibition in response to an endogenous hallucinogen, i.e., the RaRN model provides reversibility for storing and retrieving a hidden memory.
1.4.2 ENGRAMS, IMPRINTS AND MEMORY TRACES—Primitive and Subcortical
M’s first LSD experience could be a prime example of the engram, a term used by neurophysiologists and popularized by the Scientologists. To a neuropsychologist, an engram is defined as a hypothetical process producing a memory trace lodged somewhere in the unconscious to affect some central nervous system process by some unknown, unconscious process. The word, “engram” was borrowed by the scientologists to define a buried memory having unconscious adverse influence on mental and physical behavior to be monitored by skin conductivity and “cleared” by various associations. To the early 20th century biologist Richard Wolfgang Semon (1859-1918) it was a mneme, from the ancient Greek Muse of memory, Mnemosyne or Mneme, (as in mnemonic) representing much the same thing (Semon, 1921). This concept was adopted by behaviorists and extended to the idea of the “meme” as a cultural unit (Dawkins, 1976). “Imprint”, might be a another name for this kind of phenomenon, since the character of M’s LSD experience, like that of experimental animals, is argued below to be sub-cortical. The word “imprint” might better suggest the nature of this memory as encoded and non-verbal recognition of associations. The LSD recall to be described clearly conforms to these definitions of an engram, imprint or memory trace, where LSD unlocked some “storage area” within the brain and allowed impulses from this memory to flow—once again--- into thalamic and cerebral cortical areas that specialize in interpreting them as conscious awareness.
A well known example of imprinting is seen in the behavior of young geese, as they lock onto and follow the first image they see, whether it is a mother goose or a human being in a motorized hang-glider. For them, as will be argued for the fetus, it is a critical time, in which they are in a condition to receive and store the image. Beyond this time, the image is locked away in some memory crypt and their impulse to follow any figure other than the initial image is gone. Importantly, this line of research extended into Pavlovian experiments on rabbit eye-blink/sound association by Thompson and coworkers, and discussed as the scientific precedent for the “ON-OFF” nucleus analogous to the properties to be postulated here for a reticular/cerebellar nucleus interaction (Thompson and Krupa 1994). This little history is included to introduce the conclusions that 1) M’s memory is primitive and stored sub-cortically, probably in the cerebellum and 2) the concept of open/closed windows of developmental opportunity will be exemplified (Part 2).
1.4.3 On Flashbacks
The “flashbacks” testify to LSD as a mere trigger in a long process far outlasting the presence of the drug in the subject’s body. LSD may have been degraded by monoamine oxidase even before the sensations were completed during the session (see for example, Trulson and Jacobs, 1996). Presumably, the spontaneous occurrence of flashbacks at certain periods of the day reflects the same changes in the blocking nucleus to allow conscious recall of the same memory with such precision. It follows that an endogenous hallucinogen (EH) or an agent with similar molecular structure as LSD recognized the same receptor to inhibit raphe activity at the time of the flashback. On the other hand, another well-known inhibitory system could shut down raphe activity, which involves the neurotransmitter, gamma aminobutyric acid (GABA). This GABAergic system is widespread, it exists within raphe nuclei and is involved in raphe suppression (cf Nitz and Siegel, 1997). However, the issue of serotonergic inhibition by a psychoactive amine hasn’t been considered in this and many similar studies. While the GABAergic system may well be involved, it is the striking similarity of flashbacks to skull recall in the LSD session that favors the hallucinogen. It must involve a process so specific that it would require an LSD-like mechanism. The action of LSD to shut down the 5-HT raphe neurons has been shown to occur with both the direct and systemic application of LSD (Aghajanian, 1972).
The eventual disappearance of M’s flashbacks seen here raises the question about the generally pejorative view that pervades the literature (see Nichols, 2004). Flashbacks have a long negative reputation and have been associated with hallucinogen persisting perception disorder, “HPPD”-- to emphasize their character as the late appearance of “toxic” symptoms of LSD “injury” (Halpern and Pope, 2003; see Nichols, 2004 p. 135). On the other hand, flashbacks are distinguished from HPPD by others and defined as gentler echoes of the first hallucinogenic experience (Dart RC, et al eds, 2003). This view more clearly represents the flashback’s properties in M’s experience.
In contemplating why most flashback experiences with hallucinogens can be persistent, one issue stands out: The flashbacks experienced by M are subcortical in origin, as the fetus, like the mother, has no cerebrocortical memory of the birth, owing to the strong anti-cholinergic action of scopolamine on the cholinergic hippocampus and hypothalamus. Persistent flashbacks in the form of PTSD or post hallucinogenic exposure would include the adaptive efforts of the cerebral cortex to minimize the effects of fear and emotion originating from the amygdala-hippocampus axis. Obviously, the activation of the amygdala as part of the emerging memory would obscure the experience of flashbacks as signs of healing. M's mind was free of this cerebral influence.
A purely subcortical return and disappearance long after the initial LSD session could be interpreted more easily as symptoms of a healing process for erasing the memory in response to re-activating it. If it can be assumed that the activation of a toxic memory by LSD leads to a longer process of its dissolution, then the occurrence of disturbing flashbacks lasting years can be viewed as a prolonged, but unsuccessful, healing process to be expected for those not born by Twilight Sleep. The perceptual problem with this is that severe cases of flashbacks, i.e., HPPD, are disturbingly persistent over time to give the impression of permanent hallucinogenic injury. Since flashbacks and HPPD are phenomena that follow the initial hallucinogenic experience they will be viewed here as originating from the same healing process, the latter being incomplete. Moreover, posttraumatic stress disorder (PTSD) seen in severely traumatized individuals (Van der Kolk, 2006) will be included in this to comprise a trio of phenomena heralding the attempt by the organism to eliminate noxious memory. As illustrated by the properties of the RaRN mechanism, flashbacks, HPPD and PTSD are essentially the same, the latter two arising from incomplete resolution of the trauma. The persistence of the latter is accounted for by the properties of the RaRN model.
The RaRN model provides an answer to the persistence of HPPD and PTSD, since it is merely a means for opening and closing memory substrates under specific perceptual conditions. During the time of the flashback, a memory substrate is opened in response to raphe inhibition by DMT+. At this time this substrate is ready to receive additional sensory information that could reinforce the memory with new sensory input. The renewed perception of cerebral noxious symptoms attending the flashback would add to the burden of traumatic memory. For example, flashbacks are much more severe in recreational use of hallucinogens, as compared to their clinical use in therapy (Nichols, 2004). Obviously, the chaos resulting from the alarm of others would add to the open cerebral noxious contents in a recreational environment. The calmer and healing ambience of the therapeutic context would lessen the sensory influence. Indeed, in the RaRN model, the accumulation of sensory information by the open memory substrate would be additive such that new input during a flashback might add to, neutralize or displace the old. This possibility, intrinsic to the RaRN model, would account for the recent success in the treatment of PTSD with the ecstasy drug, MDMA (/www.maps.org/sys/nq.pl?id=1764&fmt=page). (Twenty out of twenty human PTSD subjects improved significantly). MDMA binds to hallucinogen receptors (Sprouse et al, 1989) and, as with LSD, would open the RaRN memory substrate to MDMA’s celebrated positive effects as new input in opposition to the noxious content of the memory. if the reinforcement was noxious, the resuming of RN blockage with the return of Ra activity would encase this new information along with the original to reinforce the trauma and lower the sensory threshold for triggering new flashbacks.
This facilitation of flashbacks in more draconian examples of trauma has been observed and explained by a model of synaptic plasticity that is hypothesized to establish “states” associated with PTSD (Perry et al, 1991). Also, this phenomenon of additional consolidation is well known in the model for treatment of PTSD with propranolol. In this case propranolol prevents additional hippocampal memory burden resulting from acetylcholine secreted by the excited amygdala. The comparison of these results with the RaRN model will be encountered in the next discussion of trauma within the subject of Twilight sleep. At this point, a similarity appears between M’s flashbacks and those flashbacks shown by clinicians to be common to posttraumatic stress disorder, PTSD. M’s flashbacks can be viewed as an experimental model that excludes the complication of cholinergic function within the hippocampus and the hypothalamus (below). It would represent an uncluttered experimental approach for the following reason: The flashbacks of severe trauma in those with PTSD may actually reflect an autonomous attempt by the organism to heal the trauma by opening the memory substrate and erase it as in M’s case -- but achieving only its reinforcement, owing to reconsolidation according to the RaRN model. With scopolamine, this reconsolidation might be avoided.
Lastly, the case for the nightly healing function of REM Sleep will be made on the basis of the flashbacks seen here as spontaneously occurring encores of the original memory recall, which disappear, never to return. Arguments are presented in this website on the page, REM Sleep Healing.
1.5 TWILIGHT SLEEP (TS)
A little probing into the advent of this obstetric protocol (Wikipedia and references therein) takes one into the turn of the 19th century, where it began in Germany with the epithet, “dammerschlaf”, introduced by Drs Richard von Steinbuchel, J. Christian Gauss and Bernard Kronig. Scopolamine was used in a mixture with morphine to produce amnesia along with morphine analgesia. Afterwards, the labor pains were entirely forgotten by the mother. In Germany the method seemed so successful that the Women's Sufferage movement in the US fought reluctant doctors and federal regulatory agencies until it was finally approved. However, poor TS management in the US in the first decade of 1900 stimulated trips to Germany by American doctors. One provision, demanded in 1915, was that, unless the Frieberg (the town where TS began) technique in Germany was followed scrupulously with detailed records and motivated nurses trained for six months, the problems encountered in American practice would continue. Eventually, the activism in favor of TS was reversed after witnesses to the birth were horrified, as the mother, strapped to the table and restrained by coverings, writhed and contorted, as if she were suffering considerably.
Dr Robert E. House, a Texas obstetrician, expanded the use of twilight sleep and took it into the 1920s, ‘30s and ‘40s, by presiding over several hundred deliveries and by teaching the method throughout the US. He gained notoriety later by diverting these efforts into the questioning of prisoners, using scopolamine as a “truth serum”. This treatment led to the release of two prisoners on death row wrongly convicted by a corrupt judicial system. Later, problems with Twilight Sleep, such as postpartum PTSD and the baby’s mental development, led to the abandonment of the procedure in the 1960s.
1.5.1 SCOPOLAMINE: DESCRIPTION AND PHARMACOLOGY
Any attempt to formulate a neural basis for M’s first LSD experience would first have to determine how the effects of scopolamine might impinge on the analysis to the extent that the proposed RaRN model would be exceptional to him, rather than more generally applicable. Scopolamine is a tropane alkaloid and shares a rather sinister history with other drugs in the same chemical family, notably cocaine and atropine. It is extracted from “deadly nigitshade”, a member of the belladonna family of plants and named by German botanists in honor of Giovanni Antonio Scopoli, a physician and naturalist, who practiced in Calvalese and Venice in the mid-late 1700s (Wikipedia). Another name, hyocine, alludes to another plant source, Hyocyamus niger found in the tropics. A more notorious name is burudanga, from the tree form of datura, Brugmansia, recognized by its large, sweet smelling flower called “angel flower”. Burudanga was slipped into the food and drink of robbery and rape victims, mainly on cruise ships. These victims are said to obey the perpetrator, even into helping with the crime and emerging afterwards with no memory of the event. More lurid and dubious accounts include of its use as and adjunct to puffer fish toxin, tetrodotoxin, said to produce the zombies of the Caribbean. Supposedly, these are people rendered helpless to resisting commands and having the symptoms of the dead, i.e., a stiff gait and undetectable heart rate. Today, it is used safely at low concentration (0.3 mg) in timed-release skin patches to alleviate nausea and vomiting from seasickness and surgical recovery. Doses approaching several milligrams can be lethal.
Two pharmacological properties of scopolamine of relevance are its strong antagonism to cholinergic processes of the muscarinic (M-3) type and its action to potentiate the effects of both morphine and hallucinogens. Cholinergic neurons are richly populated everywhere in the organism as two receptor types: nicotinic, acting rapidly at all neuromuscular junctions of peripheral muscle (sympathetic nervous system) and muscarinic, mediating slow excitatory and inhibitory responses in the brain (parasympathetic) and, notably, in smooth muscle contraction (McGeer et al, 1987, Nolte, 2002). While the contraction of skeletal muscle involves the nicotinic receptors at the neuromuscular junction, the contraction of smooth muscle also employs the muscarinic cholinergic system and would account in part for the inhibition of the mother’s uterine contractions during TS.
As a cholinergic antagonist it interferes with the memory encoding and retrieval action of the hippocampus by blocking M-3 receptors. This has been shown in humans, non-human primates and rodents (Hasselmo et al, 1996). In this regard, it is three times more potent than the classical cholinergic antagonist, atropine which is used in tiny amounts for the dilation of eye pupils for retinal examination. The hypothalamus functions through M-3 receptors as well. Blocking of the acetylcholine receptors of the hippocampus and of the hypothalamus would produce two conditions: 1) It would interfere with the hippocampus for acquiring new information and for storage of information as long-term memory within neocortical regions. Scopolamine may selectively impair learning of new information by a direct blockade of synaptic long-term potentiation (LTP), viewed as a possible learning mechanism (Sanberg et al, 2006). This will be discussed later with reference to the fetus’ development (Stage 2) and to propranolol, used in post-traumatic stress disorder (PTSD) to protect the beta-adrenergic receptors of the hippocampus from acetylcholine released by the amygdala. 2) Inhibition of the hypothalamus would block communication between limbic memory and the brainstem, which holds the physical aspects of traumatic memory in terms of the RaRN model. This would be the way in which a traumatic physical memory would remain dormant, as in M’s case, free of PTSD symptoms throughout his life.
The potentiating action of scopolamine is manifested in the amplification of morphine’s catalepsy (Kaakkola and Ahtee, 1977), a condition of muscle rigidity and persistent stable postures accompanied by lethargy and autonomic inhibition. Scopolamine’s potentiation of morphine analgesia is well known (Sperber, et al 1986). Its potentiating action for hallucinogens is particularly germane to the prediction below that an endogenous hallucinogen (EH) is secreted during late pregnancy and labor. This is seen in animal models, for example, the head-twitch (Tanaka& North 1993) and LSD catalepsy (Chiu and Mishra 1980) and in reports of the proposed mother’s uncharacteristic behavior in “normal” delivery and in the TS protocol. The actions of EH during parturition is proposed to involve the functions of the serotonin 5-HT1a and the 5-HT2a receptor subtypes that are modulated by both EH and LSD (below).
1.5.2 PREDICTED FETAL AND MATERNAL RESPONSES TO SCOPOLAMINE
As it crosses the placental barrier easily, scopolamine would repress hippocampal memory, amplify the cataleptic and analgesic effects of morphine and increase the effects of EH in regard to its proposed function and its potential for catalepsy. It is likely that the dose for the fetus was sufficiently large to produce these effects. This is unknown, but the injections were determined to be sufficient when the mother answered incoherently to a question. More injections followed throughout the labor and after the baby was born, the mother usually awoke with little or no memory of the event (the subject, M, remembers learning of this amnesia from his mother). The effects of scopolamine will be discussed now, first as a potentiator and then as a modulator of memory.
The most obvious scopolamine effect would be seen in the difficulty of fetal emergence through the birth canal. Much of this difficulty would arise from thee inhibition of the mother’s contractions by morphine and EH catalepsy, and the additional fact that smooth muscle contractions are cholinergic. In addition to its potentiation of morphine analgesia, the fetus would be cataleptic, unable to react to the efforts made for expulsion. (Later in Part 2, arguments will be presented for the necessity of active and strong fetal movement in cooperation with the mother’s contractions). Fetal movement in response to the mother’s biochemistry and contractions (discussed in Part 2) would be hampered even with sub-threshold doses of morphine. It is not hard to imagine that these effects and the well-known inhibition of the mother’s contractions by morphine would necessitate dragging the fetus out of the birth canal by the roof of its mouth.
1.5.3 THE TS MOTHER IS TRAUMATIZED. TWO KINDS OF MEMORY
The anticholinergic inhibition of the hippocampus by scopolamine accounts neatly for the mother’s amnesia of “declarative” memory, which is the voluntary recall of remembered words, facts and past events. As part of the limbic system, scopolamine prevents the hippocampus from taking new perceptual input for short-term storage and assigning it to neocortical areas for “long-term storage”. However, this inhibition doesn’t account for the fact that TS mothers are highly susceptible to postpartum post-traumatic stress disorder (PTSD) and the implication that the fear and pain of childbirth is stored as traumatic memory. Consequently, a digression into the subject of traumatic memory will be introduced at this point. Treatments according to the RaRN model will be suggested in Part 1, cont’d.
1,5,3,1 DESCANT ON THE ISSUE OF TRAUMATIC MEMORY
M’s LSD recall of simple, well defined feelings of pressure and shear in the skull has the attributes of a traumatic memory and is considered as such. Accordingly, the RaRN model may extend to the general subject of traumatic memory as a simple mechanism for opening and closing neural storage substrates for memory of this kind. This hidden memory has two attributes of trauma: First full or PTSD recall is involuntary and second, recall is recapitulative in the sense that it is a re-living of the exact sensations experienced when the traumatic insults were first imposed. The differences between full recall as in M’s case and the unresolved character of PTSD is that symptoms of the latter are modulated by adaptive counter measures by the traumatized individual.
In M’s case a memory substrate that holds the physical components of the insult is postulated here to reside within the brainstem (cerebellum). This substrate is opened to receive the insults by the suppression of raphe serotonergic neurons. On the return to their normal spontaneous firing activity, the memory substrate is closed to become hidden and to affect the individual’s life unconsciously or by expressing itself by inducing inexplicable bizarre behavior, nightmares, loss of sleep, hyper-excitability and inappropriate reactions to the environment, all of these classed under the rubric, PTSD. Trauma is a different kind of memory than the “declarative” or “narrative” category owing to its cryptic nature as an unconscious force, whose reactivation is unknown at the neural level.. It is proposed that retrieval of this memory into full conscious recall at a later time requires the re-opening of the storage by putative inactivation of raphe firing. This RaRN mechanism would apply as well to the onset of PTSD. Accordingly, it is proposed that he secretion of the endogenous hallucinogen can result from outside perceptions that are quite likely associated with the traumatic mix. These perceptions from the outside world, such as sounds, smells and sights would trigger by association the emergence of the trauma’s noxious symptoms. Many examples are known. The backfire of a passing auto’s exhaust triggers the onset of debilitating physiological changes to a Vietnam vet as he or she walks close by: an elevation in heart rate, blood pressure, confusion and momentary unconsciousness, all involuntary and recapitulative. These characteristics would apply to the TS mother as postpartum PTSD, which was one of the reasons for abandonment of this obstetric procedure.
In addition to the subcortical substrates holding the physical sensory trauma are the limbic areas that manage the psychological and emotional components of this same trauma.
Incorporation of these components involves the amygdala and the hippocampus, which are shown in Figure 3 to distinguish them from the subcortical storage substrates. The function of the amygdala is to accept emotional and fearsome perceptions, release acetylcholine to activate cholinergic receptors on the hippocampus and to add emotional and fearsome content into long term limbic memory. The resulting postulate is that the amygdala-hippocampus axis contains another long-term storage system controlled by the rostral Ra dorsalis and Ra medius in addition to mediating declarative, (cognitive) which is fetched willfully and intrinsic (non-cognitive), that range from visceral input such as an odor recalling a childhood to perceptual signals that resurrect traumatic symptoms. It is argued here that the traumatic component of hippocampal memory would be regulated by the same RaRN mechanism that regulates subcortical trauma, owing to the known serotonergic projections of the medial and dorsal raphe nuclei into the amygdala and hippocampus (see below). In this sense, a component of total memory sent into long-term neocortical storage by the hippocampus (and related organs, i.e., the anterior cingulate) is not “declarative” but “intrinsic”, as defined by the memory experts (Kandel et al, 2001 ; Nolte, 2002; McGeer, 1989; Squire, 2004; Alkon et al, 1991).
These cerebral components of trauma are in some agreement with the latest reviews from clinical research on traumatic memory, refined after decades of controversy as described in the work of Van der Kolk and Hopper (Van der Kolk et al, 2001). Earlier controversy attached to clinical studies of trauma and PTSD was based in part on confusion between these two components of traumatic memory that were not then recognized as distinguishable. These are the “narrative” and the “intrinsic” parts, now generally agreed to be separate, where he “intrinsic” persists long after the “narrative” disappears, as if the persistence of the “intrinsic” component promotes the disappearance of the “narrative”. This is borne out by the loss of image intensity in Broca’s region (language) and related parts of the cerebrum as seen by fMRI (Lanius et al, 2006).
Thus, “intrinsic” memory of the clinicians is the same as that defined here by the RaRN model: hidden and expressed as PTSD. It should be noted that not all traumatized individuals suffer from PTSD and M’s resolved LSD experience may bear on why this is so. In M’s case there was no hippocampal memory, owing to the same scopolamine anticholinergic "removal" for relieving the mother's memory. Also, scopolamine's anticholinergic action would prevent the emergence of sub-cortical pain by inhibiting hypothalamic and limbic communication with the sub-cortical memory storage substrate.
In any case, both “traumatic” and “intrinsic” are sub rosa influences on the cognitive condition of the PTSD sufferer. Based on this author’s limited knowledge of the considerable clinical literature, the focus of clinical research and its disappointments has been, as they say, “psychological trauma”. This gives the impression that the physical sensory aspect demonstrated in M’s experience and located in the subcortical brain hasn’t been considered by these workers, operating from the restrictions of interviews and experimental attempts to resurrect trauma in subjects. Here it is argued that trauma isn’t exclusively cerebral, but subcortical as well so that there are three kinds of memory relevant to discussions on trauma: declarative and traumatic (limbic) physical traumatic (subcortical), as described above. Their emphasis on “psychological trauma” is reflected by fMRI imaging solely on the cerebrum without, to this author’s knowledge, brainstem/cerebellum fMRI.
In addition to the clinical literature, recent important issues on trauma research are juxtaposed on the RaRN model in evaluating its validity in this area. First is the developing consensus that the consolidation and retrieval of memory can be explained from the research on synaptic plasticity, which has brought attention as a means of learning and development at the cellular level (xxx). Learning and memory are seen to occur as a result of the long-term depression (LTP) of a synapse in association with other elements of the memory. Conversely, long term potentiation (LTP), can occur to modify or release the memory. A good review of synaptic plasticity within the context of trauma is that of Bruce Perry and co-workers, in which all the symptoms of PTSD are clearly presented along with the clarification between the cognitive and non-cognitive domains of trauma. (Perry et al, 1991). A central notion of these authors is the formation of a “state” when a memory is recalled, which facilitates further recall with associated perceptions. This accounts for the persistence of PTSD by the (presumably normal) adaptive physiological responses to the original traumatic event. Similarly, this would account for the persistence of hallucinogenic and traumatic flashbacks described above. Moreover, the existence of this more easily accessed “state” is an attractive explanation for the quite different effects in M’s later series LSD trials, detailed in Part 2. However M’s skull sensations exemplifly the scientist’s demand for new data In this case, the persistence of a traumatic memory ended as the flashbacks gradually disappeared never to return. The more feeble nature of M’s skull trauma with its anesthesia and scopolamine anti-cholinergic effects may have been more conducive to resolution than most traumas and, as a result, more informative.
Returning now to the TS mother, her loss of limbic memory from scopolamine still leaves the problem of her postpartum PTSD and the possibility of an overt re-living of her painful labor through subliminal perceptions, as in the case of the Vietnam veteran. In other words it takes something more than the loss of accessible hippocampal memory to see the advantage of scopolamine in preventing conscious recall of the painful component of birth memory. The connection between the sensory cortex and subcortical elements that store the physiological aspects of trauma is the hypothalamus, which is also M-3 cholinergic and presumably susceptible to scopolamine. It follows that the greater advantage of scopolamine amnesia is the prevention of triggering the recall of the trauma through the main connection, the hypothalamus, which responds to perceptual signals associated with other sensory and physiological perceptions. As long as this memory persists hidden below conscious awareness by anticholinergic inhibition of the hippocampus/hypothalamus, her life will be altered by its unconscious noxious influence that remains as PTSD. Based on M’s flashbacks, full re-emergence as recapitulation would be a healing process taking place naturally to eliminate the memory --- provided the recap doesn’t reinforce the noxious contents within the memory substrate.
1.5.4 THE QUESTION OF FETAL MEMORY WITH TS
Whether the fetus would have this kind of memory normally is an issue that would involve three questions in that arise in M’s LSD recall. The first is why M’s physical skull sensations were clear and free of psychological content. The plausible answer is that that any memory mediated by the fetal hippocampus is taken entirely out of the picture with scopolamine’s anticholinergic action. The second question deals with the seeming paradox created by the postulate that one role of EH is the opening of brainstem substrates for memory consolidation, as will be argued below. One of two answers to this is that the location of the memory substrate is found in subcortical regions of the brainstem/cerebellum and is of a different kind, i.e., the same as traumatic memory that acts chronically to exert an unconscious influence on the traumatized person. Although the brainstem does involve cholinergic processes, there is no evidence that scopolamine has the same influence that it does on the hippocampus and hypothalamus. The proposal is that the key component for consolidating this kind of memory is the raphe system of nuclei, which is not cholinergic.
The third and thornier question is whether scopolamine alone, rather than EH, is responsible for the memory consolidation that actually took place at M’s birth. It is hardly conceivable that scopolamine’s inhibition of the hypothalamus would “open” subcortical memory substrates; an inverse activity relationship between the hypothalamus and brainstem elements like that between Ra and RN is not known. Another answer to both this and the previous question is that LSD is known to trigger traumatic birth recapitulation in other individuals similar to that of M, except that it is accompanied by psychological elements. The book, “Realms of the Human Unconscious” by Dr. Stanislav Grof alludes to several LSD experiences of this kind. Another example known to this author is that of a woman having had previous experiences with LSD, who, in one session, felt she was being crushed painfully all over her body, as if with a steamroller. This was associated with depression and feelings of dread and loss. As in M’s case, her crushing experience happened only once among several LSD sessions and was traced to the fact that her birth was “induced” with Pitosin, a synthetic analog of the natural steroid for uterine contraction, oxytocin. Pitosin contractions are stronger and last much longer than those induced by oxytocin and can compress the fetus to the point of collapsing lung and placental circulation. In addition, the mother and fetus are in much greater pain with Pitosin administration. Pitosin injection produces negative feedback to the hypothalamic-pituitary-adrenal axis (Cunningham et al, 2001), stopping the secretion of natural opioid analgesics during parturition.
1.5.5 Conclusion on scopolamine
In conclusion, scopolamine’s potentiation of catalepsy, as well as morphine analgesia, would account for the exceptional nature of M’s first LSD experience, reflecting the unconventional way that M entered the world. Recall of this scopolamine effect is apparent from M’s “stoned” feeling with LSD and his unwillingness to move as a preamble to the appearance of the skull sensations. However, the position chosen in this analysis is that subcortical memory consolidation of the physical sensations at birth and its later recall with LSD would have occurred with or without TS and scopolamine. Scopolamine’s main effect was twofold: To negate the psychological and emotional content of the memory recalled by M on LSD and to prevent spontaneous recall of the trauma by inhibiting the hypothalamus. This position is supported by similar hallucinogenic recalls by others born without scopolamine. Marginalizing scopolamine in the RaRN model is taken with some caution, owing to the presence of another cholinergic system in the rostral brainstem, the parabrachial nuclei, which mediate the sleep/wake cycle and REM sleep (Quattrochi et al, 1998). Relevant to the basics of the RaRN model, these nuclei communicate strongly with the thalamus and thence to the cerebral cortex (Nolte, 2002). However, this thalamic communication involves the geniculate body of the thalamus that is dedicated to carrying visuosensory and audiosensory information to cortical areas (Nolte, 2002).
There are two important considerations to emphasize about scopolamine: 1) its pharmacological effects remained as one component of a larger memory circuit containing the analgesia and the skull sensations. The implication is that this may be an associative memory akin to the learning process seen in Pavlov association research. Research in this area demonstrated the presence of an indispensable nucleus within the greater memory network that held a bi-synaptic junction between two fibers, one carrying the conditioned response and the other transmitting its trigger. In another part of this monograph, this finding is the basis for a speculative attempt to account for how the skull sensations appeared sequentially. 2) Because of the inhibition of the hypothalamus and hippocampus, re-activation of the trauma by life events perceived afterwards (as in PTSD) would not be possible. This would account for the fact that recall never occurred in the decades previous to M’s intake of LSD. Accordingly, scopolamine or a similar anti-cholinergic should be investigated as a tool for PTSD prophylaxis. I could be given to soldiers in judicious doses before a battle to prevent casual associations between injury and subsequent onsets of PTSD symptoms. The rationale for this will be illustrated graphically in Figure 9a, below.
A little probing into the advent of this obstetric protocol (Wikipedia and references therein) takes one into the turn of the 19th century, where it began in Germany with the epithet, “dammerschlaf”, introduced by Drs Richard von Steinbuchel, J. Christian Gauss and Bernard Kronig. Scopolamine was used in a mixture with morphine to produce amnesia along with morphine analgesia. Afterwards, the labor pains were entirely forgotten by the mother. In Germany the method seemed so successful that the Women's Sufferage movement in the US fought reluctant doctors and federal regulatory agencies until it was finally approved. However, poor TS management in the US in the first decade of 1900 stimulated trips to Germany by American doctors. One provision, demanded in 1915, was that, unless the Frieberg (the town where TS began) technique in Germany was followed scrupulously with detailed records and motivated nurses trained for six months, the problems encountered in American practice would continue. Eventually, the activism in favor of TS was reversed after witnesses to the birth were horrified, as the mother, strapped to the table and restrained by coverings, writhed and contorted, as if she were suffering considerably.
Dr Robert E. House, a Texas obstetrician, expanded the use of twilight sleep and took it into the 1920s, ‘30s and ‘40s, by presiding over several hundred deliveries and by teaching the method throughout the US. He gained notoriety later by diverting these efforts into the questioning of prisoners, using scopolamine as a “truth serum”. This treatment led to the release of two prisoners on death row wrongly convicted by a corrupt judicial system. Later, problems with Twilight Sleep, such as postpartum PTSD and the baby’s mental development, led to the abandonment of the procedure in the 1960s.
1.5.1 SCOPOLAMINE: DESCRIPTION AND PHARMACOLOGY
Any attempt to formulate a neural basis for M’s first LSD experience would first have to determine how the effects of scopolamine might impinge on the analysis to the extent that the proposed RaRN model would be exceptional to him, rather than more generally applicable. Scopolamine is a tropane alkaloid and shares a rather sinister history with other drugs in the same chemical family, notably cocaine and atropine. It is extracted from “deadly nigitshade”, a member of the belladonna family of plants and named by German botanists in honor of Giovanni Antonio Scopoli, a physician and naturalist, who practiced in Calvalese and Venice in the mid-late 1700s (Wikipedia). Another name, hyocine, alludes to another plant source, Hyocyamus niger found in the tropics. A more notorious name is burudanga, from the tree form of datura, Brugmansia, recognized by its large, sweet smelling flower called “angel flower”. Burudanga was slipped into the food and drink of robbery and rape victims, mainly on cruise ships. These victims are said to obey the perpetrator, even into helping with the crime and emerging afterwards with no memory of the event. More lurid and dubious accounts include of its use as and adjunct to puffer fish toxin, tetrodotoxin, said to produce the zombies of the Caribbean. Supposedly, these are people rendered helpless to resisting commands and having the symptoms of the dead, i.e., a stiff gait and undetectable heart rate. Today, it is used safely at low concentration (0.3 mg) in timed-release skin patches to alleviate nausea and vomiting from seasickness and surgical recovery. Doses approaching several milligrams can be lethal.
Two pharmacological properties of scopolamine of relevance are its strong antagonism to cholinergic processes of the muscarinic (M-3) type and its action to potentiate the effects of both morphine and hallucinogens. Cholinergic neurons are richly populated everywhere in the organism as two receptor types: nicotinic, acting rapidly at all neuromuscular junctions of peripheral muscle (sympathetic nervous system) and muscarinic, mediating slow excitatory and inhibitory responses in the brain (parasympathetic) and, notably, in smooth muscle contraction (McGeer et al, 1987, Nolte, 2002). While the contraction of skeletal muscle involves the nicotinic receptors at the neuromuscular junction, the contraction of smooth muscle also employs the muscarinic cholinergic system and would account in part for the inhibition of the mother’s uterine contractions during TS.
As a cholinergic antagonist it interferes with the memory encoding and retrieval action of the hippocampus by blocking M-3 receptors. This has been shown in humans, non-human primates and rodents (Hasselmo et al, 1996). In this regard, it is three times more potent than the classical cholinergic antagonist, atropine which is used in tiny amounts for the dilation of eye pupils for retinal examination. The hypothalamus functions through M-3 receptors as well. Blocking of the acetylcholine receptors of the hippocampus and of the hypothalamus would produce two conditions: 1) It would interfere with the hippocampus for acquiring new information and for storage of information as long-term memory within neocortical regions. Scopolamine may selectively impair learning of new information by a direct blockade of synaptic long-term potentiation (LTP), viewed as a possible learning mechanism (Sanberg et al, 2006). This will be discussed later with reference to the fetus’ development (Stage 2) and to propranolol, used in post-traumatic stress disorder (PTSD) to protect the beta-adrenergic receptors of the hippocampus from acetylcholine released by the amygdala. 2) Inhibition of the hypothalamus would block communication between limbic memory and the brainstem, which holds the physical aspects of traumatic memory in terms of the RaRN model. This would be the way in which a traumatic physical memory would remain dormant, as in M’s case, free of PTSD symptoms throughout his life.
The potentiating action of scopolamine is manifested in the amplification of morphine’s catalepsy (Kaakkola and Ahtee, 1977), a condition of muscle rigidity and persistent stable postures accompanied by lethargy and autonomic inhibition. Scopolamine’s potentiation of morphine analgesia is well known (Sperber, et al 1986). Its potentiating action for hallucinogens is particularly germane to the prediction below that an endogenous hallucinogen (EH) is secreted during late pregnancy and labor. This is seen in animal models, for example, the head-twitch (Tanaka& North 1993) and LSD catalepsy (Chiu and Mishra 1980) and in reports of the proposed mother’s uncharacteristic behavior in “normal” delivery and in the TS protocol. The actions of EH during parturition is proposed to involve the functions of the serotonin 5-HT1a and the 5-HT2a receptor subtypes that are modulated by both EH and LSD (below).
1.5.2 PREDICTED FETAL AND MATERNAL RESPONSES TO SCOPOLAMINE
As it crosses the placental barrier easily, scopolamine would repress hippocampal memory, amplify the cataleptic and analgesic effects of morphine and increase the effects of EH in regard to its proposed function and its potential for catalepsy. It is likely that the dose for the fetus was sufficiently large to produce these effects. This is unknown, but the injections were determined to be sufficient when the mother answered incoherently to a question. More injections followed throughout the labor and after the baby was born, the mother usually awoke with little or no memory of the event (the subject, M, remembers learning of this amnesia from his mother). The effects of scopolamine will be discussed now, first as a potentiator and then as a modulator of memory.
The most obvious scopolamine effect would be seen in the difficulty of fetal emergence through the birth canal. Much of this difficulty would arise from thee inhibition of the mother’s contractions by morphine and EH catalepsy, and the additional fact that smooth muscle contractions are cholinergic. In addition to its potentiation of morphine analgesia, the fetus would be cataleptic, unable to react to the efforts made for expulsion. (Later in Part 2, arguments will be presented for the necessity of active and strong fetal movement in cooperation with the mother’s contractions). Fetal movement in response to the mother’s biochemistry and contractions (discussed in Part 2) would be hampered even with sub-threshold doses of morphine. It is not hard to imagine that these effects and the well-known inhibition of the mother’s contractions by morphine would necessitate dragging the fetus out of the birth canal by the roof of its mouth.
1.5.3 THE TS MOTHER IS TRAUMATIZED. TWO KINDS OF MEMORY
The anticholinergic inhibition of the hippocampus by scopolamine accounts neatly for the mother’s amnesia of “declarative” memory, which is the voluntary recall of remembered words, facts and past events. As part of the limbic system, scopolamine prevents the hippocampus from taking new perceptual input for short-term storage and assigning it to neocortical areas for “long-term storage”. However, this inhibition doesn’t account for the fact that TS mothers are highly susceptible to postpartum post-traumatic stress disorder (PTSD) and the implication that the fear and pain of childbirth is stored as traumatic memory. Consequently, a digression into the subject of traumatic memory will be introduced at this point. Treatments according to the RaRN model will be suggested in Part 1, cont’d.
1,5,3,1 DESCANT ON THE ISSUE OF TRAUMATIC MEMORY
M’s LSD recall of simple, well defined feelings of pressure and shear in the skull has the attributes of a traumatic memory and is considered as such. Accordingly, the RaRN model may extend to the general subject of traumatic memory as a simple mechanism for opening and closing neural storage substrates for memory of this kind. This hidden memory has two attributes of trauma: First full or PTSD recall is involuntary and second, recall is recapitulative in the sense that it is a re-living of the exact sensations experienced when the traumatic insults were first imposed. The differences between full recall as in M’s case and the unresolved character of PTSD is that symptoms of the latter are modulated by adaptive counter measures by the traumatized individual.
In M’s case a memory substrate that holds the physical components of the insult is postulated here to reside within the brainstem (cerebellum). This substrate is opened to receive the insults by the suppression of raphe serotonergic neurons. On the return to their normal spontaneous firing activity, the memory substrate is closed to become hidden and to affect the individual’s life unconsciously or by expressing itself by inducing inexplicable bizarre behavior, nightmares, loss of sleep, hyper-excitability and inappropriate reactions to the environment, all of these classed under the rubric, PTSD. Trauma is a different kind of memory than the “declarative” or “narrative” category owing to its cryptic nature as an unconscious force, whose reactivation is unknown at the neural level.. It is proposed that retrieval of this memory into full conscious recall at a later time requires the re-opening of the storage by putative inactivation of raphe firing. This RaRN mechanism would apply as well to the onset of PTSD. Accordingly, it is proposed that he secretion of the endogenous hallucinogen can result from outside perceptions that are quite likely associated with the traumatic mix. These perceptions from the outside world, such as sounds, smells and sights would trigger by association the emergence of the trauma’s noxious symptoms. Many examples are known. The backfire of a passing auto’s exhaust triggers the onset of debilitating physiological changes to a Vietnam vet as he or she walks close by: an elevation in heart rate, blood pressure, confusion and momentary unconsciousness, all involuntary and recapitulative. These characteristics would apply to the TS mother as postpartum PTSD, which was one of the reasons for abandonment of this obstetric procedure.
In addition to the subcortical substrates holding the physical sensory trauma are the limbic areas that manage the psychological and emotional components of this same trauma.
Incorporation of these components involves the amygdala and the hippocampus, which are shown in Figure 3 to distinguish them from the subcortical storage substrates. The function of the amygdala is to accept emotional and fearsome perceptions, release acetylcholine to activate cholinergic receptors on the hippocampus and to add emotional and fearsome content into long term limbic memory. The resulting postulate is that the amygdala-hippocampus axis contains another long-term storage system controlled by the rostral Ra dorsalis and Ra medius in addition to mediating declarative, (cognitive) which is fetched willfully and intrinsic (non-cognitive), that range from visceral input such as an odor recalling a childhood to perceptual signals that resurrect traumatic symptoms. It is argued here that the traumatic component of hippocampal memory would be regulated by the same RaRN mechanism that regulates subcortical trauma, owing to the known serotonergic projections of the medial and dorsal raphe nuclei into the amygdala and hippocampus (see below). In this sense, a component of total memory sent into long-term neocortical storage by the hippocampus (and related organs, i.e., the anterior cingulate) is not “declarative” but “intrinsic”, as defined by the memory experts (Kandel et al, 2001 ; Nolte, 2002; McGeer, 1989; Squire, 2004; Alkon et al, 1991). These cerebral components of trauma are in some agreement with the latest reviews from clinical research on traumatic memory, refined after decades of controversy as described in the work of Van der Kolk and Hopper (Van der Kolk et al, 2001). Earlier controversy attached to clinical studies of trauma and PTSD was based in part on confusion between these two components of traumatic memory that were not then recognized as distinguishable. These are the “narrative” and the “intrinsic” parts, now generally agreed to be separate, where he “intrinsic” persists long after the “narrative” disappears, as if the persistence of the “intrinsic” component promotes the disappearance of the “narrative”. This is borne out by the loss of image intensity in Broca’s region (language) and related parts of the cerebrum as seen by fMRI (Lanius et al, 2006).
Thus, “intrinsic” memory of the clinicians is the same as that defined here by the RaRN model: hidden and expressed as PTSD. It should be noted that not all traumatized individuals suffer from PTSD and M’s resolved LSD experience may bear on why this is so. In M’s case there was no hippocampal memory, owing to the same scopolamine anticholinergic "removal" for relieving the mother's memory. Also, scopolamine's anticholinergic action would prevent the emergence of sub-cortical pain by inhibiting hypothalamic and limbic communication with the sub-cortical memory storage substrate.
In any case, both “traumatic” and “intrinsic” are sub rosa influences on the cognitive condition of the PTSD sufferer. Based on this author’s limited knowledge of the considerable clinical literature, the focus of clinical research and its disappointments has been, as they say, “psychological trauma”. This gives the impression that the physical sensory aspect demonstrated in M’s experience and located in the subcortical brain hasn’t been considered by these workers, operating from the restrictions of interviews and experimental attempts to resurrect trauma in subjects. Here it is argued that trauma isn’t exclusively cerebral, but subcortical as well so that there are three kinds of memory relevant to discussions on trauma: declarative and traumatic (limbic) physical traumatic (subcortical), as described above. Their emphasis on “psychological trauma” is reflected by fMRI imaging solely on the cerebrum without, to this author’s knowledge, brainstem/cerebellum fMRI.
In addition to the clinical literature, recent important issues on trauma research are juxtaposed on the RaRN model in evaluating its validity in this area. First is the developing consensus that the consolidation and retrieval of memory can be explained from the research on synaptic plasticity, which has brought attention as a means of learning and development at the cellular level (xxx). Learning and memory are seen to occur as a result of the long-term depression (LTP) of a synapse in association with other elements of the memory. Conversely, long term potentiation (LTP), can occur to modify or release the memory. A good review of synaptic plasticity within the context of trauma is that of Bruce Perry and co-workers, in which all the symptoms of PTSD are clearly presented along with the clarification between the cognitive and non-cognitive domains of trauma. (Perry et al, 1991). A central notion of these authors is the formation of a “state” when a memory is recalled, which facilitates further recall with associated perceptions. This accounts for the persistence of PTSD by the (presumably normal) adaptive physiological responses to the original traumatic event. Similarly, this would account for the persistence of hallucinogenic and traumatic flashbacks described above. Moreover, the existence of this more easily accessed “state” is an attractive explanation for the quite different effects in M’s later series LSD trials, detailed in Part 2. However M’s skull sensations exemplifly the scientist’s demand for new data In this case, the persistence of a traumatic memory ended as the flashbacks gradually disappeared never to return. The more feeble nature of M’s skull trauma with its anesthesia and scopolamine anti-cholinergic effects may have been more conducive to resolution than most traumas and, as a result, more informative.
Returning now to the TS mother, her loss of limbic memory from scopolamine still leaves the problem of her postpartum PTSD and the possibility of an overt re-living of her painful labor through subliminal perceptions, as in the case of the Vietnam veteran. In other words it takes something more than the loss of accessible hippocampal memory to see the advantage of scopolamine in preventing conscious recall of the painful component of birth memory. The connection between the sensory cortex and subcortical elements that store the physiological aspects of trauma is the hypothalamus, which is also M-3 cholinergic and presumably susceptible to scopolamine. It follows that the greater advantage of scopolamine amnesia is the prevention of triggering the recall of the trauma through the main connection, the hypothalamus, which responds to perceptual signals associated with other sensory and physiological perceptions. As long as this memory persists hidden below conscious awareness by anticholinergic inhibition of the hippocampus/hypothalamus, her life will be altered by its unconscious noxious influence that remains as PTSD. Based on M’s flashbacks, full re-emergence as recapitulation would be a healing process taking place naturally to eliminate the memory --- provided the recap doesn’t reinforce the noxious contents within the memory substrate.
1.5.4 THE QUESTION OF FETAL MEMORY WITH TS
Whether the fetus would have this kind of memory normally is an issue that would involve three questions in that arise in M’s LSD recall. The first is why M’s physical skull sensations were clear and free of psychological content. The plausible answer is that that any memory mediated by the fetal hippocampus is taken entirely out of the picture with scopolamine’s anticholinergic action. The second question deals with the seeming paradox created by the postulate that one role of EH is the opening of brainstem substrates for memory consolidation, as will be argued below. One of two answers to this is that the location of the memory substrate is found in subcortical regions of the brainstem/cerebellum and is of a different kind, i.e., the same as traumatic memory that acts chronically to exert an unconscious influence on the traumatized person. Although the brainstem does involve cholinergic processes, there is no evidence that scopolamine has the same influence that it does on the hippocampus and hypothalamus. The proposal is that the key component for consolidating this kind of memory is the raphe system of nuclei, which is not cholinergic.
The third and thornier question is whether scopolamine alone, rather than EH, is responsible for the memory consolidation that actually took place at M’s birth. It is hardly conceivable that scopolamine’s inhibition of the hypothalamus would “open” subcortical memory substrates; an inverse activity relationship between the hypothalamus and brainstem elements like that between Ra and RN is not known. Another answer to both this and the previous question is that LSD is known to trigger traumatic birth recapitulation in other individuals similar to that of M, except that it is accompanied by psychological elements. The book, “Realms of the Human Unconscious” by Dr. Stanislav Grof alludes to several LSD experiences of this kind. Another example known to this author is that of a woman having had previous experiences with LSD, who, in one session, felt she was being crushed painfully all over her body, as if with a steamroller. This was associated with depression and feelings of dread and loss. As in M’s case, her crushing experience happened only once among several LSD sessions and was traced to the fact that her birth was “induced” with Pitosin, a synthetic analog of the natural steroid for uterine contraction, oxytocin. Pitosin contractions are stronger and last much longer than those induced by oxytocin and can compress the fetus to the point of collapsing lung and placental circulation. In addition, the mother and fetus are in much greater pain with Pitosin administration. Pitosin injection produces negative feedback to the hypothalamic-pituitary-adrenal axis (Cunningham et al, 2001), stopping the secretion of natural opioid analgesics during parturition.
1.5.5 Conclusion on scopolamine
In conclusion, scopolamine’s potentiation of catalepsy, as well as morphine analgesia, would account for the exceptional nature of M’s first LSD experience, reflecting the unconventional way that M entered the world. Recall of this scopolamine effect is apparent from M’s “stoned” feeling with LSD and his unwillingness to move as a preamble to the appearance of the skull sensations. However, the position chosen in this analysis is that subcortical memory consolidation of the physical sensations at birth and its later recall with LSD would have occurred with or without TS and scopolamine. Scopolamine’s main effect was twofold: To negate the psychological and emotional content of the memory recalled by M on LSD and to prevent spontaneous recall of the trauma by inhibiting the hypothalamus. This position is supported by similar hallucinogenic recalls by others born without scopolamine. Marginalizing scopolamine in the RaRN model is taken with some caution, owing to the presence of another cholinergic system in the rostral brainstem, the parabrachial nuclei, which mediate the sleep/wake cycle and REM sleep (Quattrochi et al, 1998). Relevant to the basics of the RaRN model, these nuclei communicate strongly with the thalamus and thence to the cerebral cortex (Nolte, 2002). However, this thalamic communication involves the geniculate body of the thalamus that is dedicated to carrying visuosensory and audiosensory information to cortical areas (Nolte, 2002).
There are two important considerations to emphasize about scopolamine: 1) its pharmacological effects remained as one component of a larger memory circuit containing the analgesia and the skull sensations. The implication is that this may be an associative memory akin to the learning process seen in Pavlov association research. Research in this area demonstrated the presence of an indispensable nucleus within the greater memory network that held a bi-synaptic junction between two fibers, one carrying the conditioned response and the other transmitting its trigger. In another part of this monograph, this finding is the basis for a speculative attempt to account for how the skull sensations appeared sequentially. 2) Because of the inhibition of the hypothalamus and hippocampus, re-activation of the trauma by life events perceived afterwards (as in PTSD) would not be possible. This would account for the fact that recall never occurred in the decades previous to M’s intake of LSD. Accordingly, scopolamine or a similar anti-cholinergic should be investigated as a tool for PTSD prophylaxis. I could be given to soldiers in judicious doses before a battle to prevent casual associations between injury and subsequent onsets of PTSD symptoms. The rationale for this will be illustrated graphically in Figure 9a, below.
1.6 THE MOLECULAR-BIOLOGICAL LANDSCAPE
The following narrative will appear daunting to some, owing to the technical jargon unfamiliar to the general reader. Unfamiliar words and concepts are being prepared as hyperlinks to descriptions that should be helpful. Otherwise, it may be better to skip this portion and proceed to the section, “Which Receptors?” or further to “The Raphe Nuclei”.
Keeping in mind the disclaimer already made above about species difference, the emergence of M’s hidden memory must have resulted from the binding of LSD to its preferred receptors that are broadly distributed throughout brain and body. Receptors relevant to hallucinogens and related to other neurotransmitter systems are found in the synaptic junctions for communication between neurons, where the axon of one neuron communicates to the dendrite of another across the synapse. LSD is a ligand almost exclusively to receptor subtypes of the serotonergic system of neurons that functions in broadly distributed areas of the brain. The natural ligand of all these receptors is serotonin, abbreviated as 5-HT to illustrate that it is really 5-hydroxytryptamine, which is made in the body from the amino acid, tryptophan. Similar psychotropic drugs based on this structure are of the indole class, as opposed to the hallucinogens of the phenethylamine class exemplified by mescaline (see Glennon, 1987). Of course, different receptor subtypes, for example the 5-HT2 a, b, c, --- series and likewise for the 5-HT1 series, in addition to 5-HT3, etc., are spread globally and several bind to hallucinogens. The preferred receptors for LSD are: 5-HT1a/1b/1d, 5-HT2a/2c, 5-HT5a, 6 and 7 (see Nichols, 2004 p. 161 and cited references therein). LSD and similar indole or tryptamine molecules have a high affinity for the 5-HT1a receptor, which is the focus of the RaRN model (McKenna et al, 1990). Unlike the indoles, the phenethylamine hallucinogens don't bind to the 1a, and prefer the 2a/2c. The 5-HT2a and 2c receptors found in the cortical layers of the pre-frontal cortex mediate the famous hallucinogenic effect and the most potent drug in this regard is LSD. This may be related to the response of excitatory glutamate receptors connected to the function of 2a/2c. Notably, the 1a and 2a receptors are affected by other neurotransmitter systems, e.g., the cholinergic and GABAergic influence on he 5-HT1a receptor (Haddjeri et al, 2000). Significant neurotransmitter systems other than 5-HT respond to LSD. The dopamine (DA) system within the caudate nucleus and the nucleus accumbens is well known for its relationship to addiction at these pleasure centers and for its alleviation of Parkinson's symptoms including another site, the substantia nigra. The caudate and the acumbens have binding sites for indoles. While LSD binds to both DA receptors, D1 and D2, with a preference for the latter, it is not addictive.
The following narrative will appear daunting to some, owing to the technical jargon unfamiliar to the general reader. Unfamiliar words and concepts are being prepared as hyperlinks to descriptions that should be helpful. Otherwise, it may be better to skip this portion and proceed to the section, “Which Receptors?” or further to “The Raphe Nuclei”.
Keeping in mind the disclaimer already made above about species difference, the emergence of M’s hidden memory must have resulted from the binding of LSD to its preferred receptors that are broadly distributed throughout brain and body. Receptors relevant to hallucinogens and related to other neurotransmitter systems are found in the synaptic junctions for communication between neurons, where the axon of one neuron communicates to the dendrite of another across the synapse. LSD is a ligand almost exclusively to receptor subtypes of the serotonergic system of neurons that functions in broadly distributed areas of the brain. The natural ligand of all these receptors is serotonin, abbreviated as 5-HT to illustrate that it is really 5-hydroxytryptamine, which is made in the body from the amino acid, tryptophan. Similar psychotropic drugs based on this structure are of the indole class, as opposed to the hallucinogens of the phenethylamine class exemplified by mescaline (see Glennon, 1987). Of course, different receptor subtypes, for example the 5-HT2 a, b, c, --- series and likewise for the 5-HT1 series, in addition to 5-HT3, etc., are spread globally and several bind to hallucinogens. The preferred receptors for LSD are: 5-HT1a/1b/1d, 5-HT2a/2c, 5-HT5a, 6 and 7 (see Nichols, 2004 p. 161 and cited references therein). LSD and similar indole or tryptamine molecules have a high affinity for the 5-HT1a receptor, which is the focus of the RaRN model (McKenna et al, 1990). Unlike the indoles, the phenethylamine hallucinogens don't bind to the 1a, and prefer the 2a/2c. The 5-HT2a and 2c receptors found in the cortical layers of the pre-frontal cortex mediate the famous hallucinogenic effect and the most potent drug in this regard is LSD. This may be related to the response of excitatory glutamate receptors connected to the function of 2a/2c. Notably, the 1a and 2a receptors are affected by other neurotransmitter systems, e.g., the cholinergic and GABAergic influence on he 5-HT1a receptor (Haddjeri et al, 2000). Significant neurotransmitter systems other than 5-HT respond to LSD. The dopamine (DA) system within the caudate nucleus and the nucleus accumbens is well known for its relationship to addiction at these pleasure centers and for its alleviation of Parkinson's symptoms including another site, the substantia nigra. The caudate and the acumbens have binding sites for indoles. While LSD binds to both DA receptors, D1 and D2, with a preference for the latter, it is not addictive.
1.6.1 IDENTIFYING AND SORTING RECEPTOR SUBTYPES.
Because they are referred to frequently in the text, two well-known methods for identifying receptor subtypes will be described at this point. The first is the measurement of ligand binding to a receptor in the presence of a competitive ligand, which can be measured by its radioactivity. A standard method for determining the affinity and selection of a hallucinogen for, say, the 5-HT2a receptor depends on the ability of LSD to displace the 2a antagonist, ketanserin, in the radioactive form, (H3-(tritiated) ketanserin). The receptors are prepared in dispersed emulsions rich in the receptor subtype, most often from the rat frontal cortex. Several tubes containing this preparation, the antagonist and different concentrations of LSD are filtered, washed and counted in a radioactivity counter to produce a decreased in radioactivity counts as a function of LSD concentration. This method yields the affinity of LSD or the affinity of any other hallucinogen of analogous structure for the receptor as a number (binding constant) used for comparison.
The second method, called discriminative cue selection, is based on the influence of a drug on an animal trained to choose one of two levers that provide a reward (Glennon, et al, 1983). If the rat is pretreated for a time with a drug (like LSD) and lever A alone provides the reward, then the rat will learn by association between the discriminative cue (LSD effect) and lever A for 90% selection accuracy. If the training is done with the LSD vehicle (saline), the B lever will provide the reward. After some weeks of this training, both levers provide the reward and the rat will select A or B depending on the condition it is in. The rat on LSD will fail to select lever A over B when given the LSD antagonist, ketanserin, and discrimination between the two levers is lost. This method can be extended to the use of agonists (promoters) to the drug. Cross reactivity between other receptor subtypes can be studied by this sensitive and powerful method. For example, the 5-HT2a and 2c receptors oppose each other in diminishing discriminative cues for cocaine. The combination of a 2a antagonist with a 2c agonist diminishes significantly the discriminative cues for craving cocaine or relapsing.
1.6.2 WHICH RECEPTORS?
For M’s LSD recall of skull sensations, the most highly suspect LSD receptors are the 5-HT2a and the 5-HT1a, which are thought to exhibit quite different properties with LSD binding. The 5-HT2a receptors mediate an excitatory response to the pyramidal neurons within the cortical layers of the prefrontal cortex. It is these cortical receptors that are thought to be responsible for hallucinogenic inebriation, e.g., the visionary, reflective and spiritual realms. By contrast, the 5-HT1a subtype mediates an inhibitory response and, although the 5-HT1a receptors co-exist with cortical 5-HT2a receptors in the cerebral cortex, their location for specific brainstem functioning is exclusively within the raphe nuclei of the brainstem’s reticular formation. Apparently, LSD- 5-HT1a binding is non-hallucinogenic. For example, a structural analog of LSD, lisuride, is a potent and selective agonist for 5-HT1a and is non-hallucinogenic (Egan et al., 1998, Marona-Lewicka et al., 2002). Binding of LSD to the 5-HT1a receptor in the raphe nucleus strongly inhibits the firing of its serotonergic neurons by direct or systemic application (Aghajanian et al, 1968, 1970, 1972). Endogenous hallucinogens, notably dimethyltryptamine and 5-methoxy DMT, inhibit the firing of the dorsal raphe serotonergic axons (Aghajanian and Haigler, 1975). These hallucinogens are considered as agonists (promoters) although raphe activity is suppressed. Does this suggest that the natural function of serotonin for this receptor is to inhibit the raphe? Check out the link, agonists and antagonists.
How would one account for the fact that hallucinogen binding to the 1a receptor inhibits serotoninergic neurons within that raphe nucleus, thereby releasing other systems inhibited by their axons? In accounting for M’s LSD results in terms of the RaRN model, other neurotransmitter systems within the raphe must be considered: the inhibitory gamma amino butyrate (GABA) receptors, the excitatory alpha-1 adrenergic receptors and the excitatory glutamate receptors. One explanation would be that the LSD-bound 1a receptor activates the GABAergic suppression of these 5-HT neurons. Although this is unlikely (Aghajanian et al, 1972) there are several examples of this on issues of birth (Kaura et al, 2007) limbic (hippocampal) activity (Li et al, 2005) and REM sleep (Torterolo et al, 2000). These will be discussed later with respect to parturition with regard to activation of the hypothalamus. In any case, the interpretation will proceed with the fact that the indole hallucinogens suppress serotonergic neurons in the raphe nuclei at the 5-HT1a receptor, hypothetically to dis-inhibit reticular nuclei that control memory access in the brainstem. These same hallucinogens are excitatory in the thalamocortical regions as to their binding to the 5-HT2a/2c/glutamate complex.
1.6.3 5-HT1A AND 5-HT2A CONTRIBUTIONS
The selection of a key receptor such as the raphe 5-HT1a is also shadowed by additional knowledge of receptor interactions that can diminish its certainty. The 5-HT 1a and 2a functions often appear to interact and can’t be separated completely in certain cue discrimination studies. In addition, the 2a function is clearly tied to the glutamate and dopamine receptors. Glutamate is released in the prefrontal cortex by a 2a agonist as a postulated mechanism for cortical excitation (Nichols, 2004 p. 147). While LSD discriminative cues involve the 2a receptor, momentary pre-treatment with LSD well before the test are mediated by the dopamine D2 receptor. In addition, LSD activates gene expression and metabolism at 2a sites. Another important research area is the influence hallucinogens have on changes in genetic expression, examined mainly by c-Fos immuno-histology, a break-through method that can determine new RNA synthesis at any given brain site (see the Biology of Parturition, below). With these complicating issues in mind, the model to be presented grows from the simpler basic idea that LSD binds to 5-HT1a to stop the firing of raphe 5-HT neurons and unblock nuclei of brainstem reticular formation. The concurrent involvement of 5-HT2a at birth is also important as a mental bolster for the mother and for activation of the hypothalamus (see below).
The consensus hallucinogenic 5-HT2a effect M experienced early in the session was dream-like and very brief. This little show was completely over before the sensory recapitulation that dominated throughout the rest of the LSD session. This is consistent with the findings that LSD is not a strong functional ligand for the 5-HT2a receptor (see McClue et al, 1989 and references therein), although LSD inebriation is more intense than that of other hallucinogens. Also, the opposition by the inhibitory 5-HT1a receptors in the same prefrontal cortical area would contribute to the brevity of this cerebral effect. The 5-HT1a receptor is found throughout the thalamocortical areas and coexists with 5-HT2a receptors in cortical pyramidal layers (however, see Nichols, 2004). Therefore, the memory of skull sensations is postulated to be located somewhere within a brainstem nucleus (probably the cerebellum) under the control of the raphe 5-HT1a receptor and DMT (or a derivative, 5-methoxy-N,N-dimethyltryptamine) as the endogenous raphe inhibitor. These and other possibilities for the identity of the endogenous hallucinogen are considered in detail below in 1.9, “What is the endogenous hallucinogen?”.
Support for 5-HT1a in functional venues such as birth and trauma in humans or primates might be found by extrapolation from similar 2a venues in rat models. The antagonist to the 5-HT2a receptor (ketanserin) blocks the rat’s cue to selecting the LSD lever in the discrimination test (above), but not for our much closer relative, the monkey (Nichols, 2004; Nielsen, 1985). Also, a mixed 5-HT1a/5-HT2 agonist, 5-methoxy DMT (one of the proposed endogenous hallucinogens) did provide the monkey with the LSD cue, reflecting the (dim) possibility that the 5-HT1a receptor for us primates may have the higher priority for LSD or EH function. Thus, certain functions involving 2a in the rat might involve the 1a in primates. For example, the secretion of supportive pituitary hormones at birth requires activation of the nuclei within the hypothalamus. As this involves 2a in the rat, it could involve 1a in the human at parturition (see Biology of Parturition, below). Aside from this hypothalamic suggestion, the receptor involved in both M’s LSD recall and the EH mediated planting of the memory at birth is proposed to be the (non-hallucinogenic) 5-HT1a. In addition to the foregoing functional identification of individual raphe nuclei, the finding of high similarity between the indoles, DMT and LSD, as strong ligands to this receptor is consistent (Glennon et al., 1986; Deliganis AV, Pierce PA and Peroutka SJ (1991) Differential interactions of dimethyltryptamine (DMT) with 5-HT1A and 5-HT2 receptors Biochemical Pharmacology
Volume 41, Issue 11, 1 June 1991, Pages 1739-1744 .
1.6.4 THE RAPHE NUCLEI
As shown in Figure 4, seven or eight raphe nuclei are distributed vertically along the midline seam of the brainstem reticular formation. The R. linearius, R. dorsalis and R. medius are the rostral (upper) nuclei that project most of their axons into the forebrain hypothalamus and the memory areas of the limbic system, the hippocampus and the amygdala. The more caudal (lower) nuclei are the R.pontis, R. magnus, R. pallidus and R. obscuris, which serve the cerebellum and the peripheral and visceral functions.
M’s experience of peristalsis early In his LSD session would involve the R. pallidus and R. obscuris within the medulla (Kaneko et al, 1998, Yvette et al 1991) and the inaugurating experience of opiate anesthesia, might correspond to R. magnus generally known to mediate the suppression of pain by opiates, whether administered or endogenous (Mason et al, 2007), however, see Gao et al, 1998. R. magnus receives input from the periaqueductal grey, a repository of opiate receptors that begins in the midbrain and descends down the spinal column (Nolte, 2002). The identity of raphe nuclei corresponding to M’s palate and skull sensations would be located in the lower pons to upper medulla region (probably R. pontis and R. magnus) and their caudal (lower) position in the brainstem is consistent with the location of the sensory nucleus that received M’s palate pressure at birth (discussed below). Also, R. magnus at this position in the rat medulla has an “on-off” property in firing its serotonergic axons (Foo and Mason, 2003) and is inhibited by LSD, as are the R. pallidus and R. obscuris in the rat (Briggs, 1977)). Prolonged LSD administration to R. magnus inhibits, but down-regulates its receptor, while that of methoxy-DMT does not, which is consistent with the differences in tolerance between these two, and between LSD and DMT (Larson, 1984).The serotonergic projections of raphe nuclei are widespread in the central nervous system (CNS) as shown in the sketch of Figure 4a. (Many thanks to John Nolte, author, and Laura Steward of the publisher, Mosby/Elsevier for their kind permission to use this image from Nolte, 2002.)
Of additional importance to this discussion are the projections to the amygdala, hippocampus that are relevant to comments on psychological trauma, while those to the hypothalamus and thalamus will be discussed with respect to secretions and mental state during parturition.This correspondence between these consensus functions of some raphe nuclei and the physical sensations experienced by M does constitute support that the key elements for encryption of the palate and skull sensations involve brainstem nuclei. In addition, the nature of memory recall was physical, involuntary and recapitulative, in contrast to the intrinsic and extrinsic or declarative memory that is accessible willfully or by visceral cues, as discussed below in the section on scopolamine (Kandel, et al 2001). The limbic brain areas, as well as the rostral raphe nuclei can be excluded as elements of this particular encryption mechanism, at least initially. The rostral raphe projections to limbic areas of the brain would be similarly involved with psychological/emotional memories. not the physical re-living of sensations arising with M’s recall. The memory M experienced was devoid of emotional content as accounted for by the action of scopolamine.
Earlier, it was noted that these involuntary and autonomous sensations continued spontaneously for some weeks as recurrences or “flashbacks” until they disappeared. They often appeared within an hour or two after awakening from a night’s sleep. A number of research reports on the involvement of the dorsal raphe nucleus at the onset of REM sleep suggest that the morning flashbacks may have been stimulated by reticular activation related to this process of raphe inhibition (Saphier, 1991). However, there is some controversy regarding the function of raphe nuclei in REM sleep (Rodrigo-Argulo et al, 2000; see Notes). These authors question the involvement of raphe nuclei altogether on the basis of retrograde dye transfer along axonal paths in the brainstem.
1.7 THE ANATOMICAL PATHWAY
Obviously, to this writer of residual mania, the foregoing is enough on the RaRN model to start a land-rush frenzy of activity in obstetric hospitals and laboratories testing its validity and expanding on it as a paradigm to open new therapeutic opportunities. There will be more on this in due course. At this point the RaRN model must run the gauntlet of anatomy by following sensory impulse flow between memory “storage” and the thalamocortical areas that provide conscious interpretation. The changes in impulse traffic imposed by LSD or EH will be shown and the focus will be on M’s palate sensations.
1.7.1 FROM PALATE TO THE BRAINSTEM
In this Twilight Sleep birth, the obstetrician’s fingers impinge upon the pressure nociceptors in M’s palate sending impulses along fibers through the jugular foramen directly to the pons-medulla area of the brainstem. These fibers join the sensory component of the pharyngeal branch of the glossopharyngeal nerve, Cranial nerve (CN) IX (Diamond et al.,1985, Nolte, 2002).
This information is sent directly to the Nucleus Solitarius (NS), a sensory relay station in the lower pons and upper medulla that is part of the “solitary tract”. A gross illustration of the route between palate and the brainstem area of NS is shown as an MRI scan in Figure 5. Sensory components of cranial nerves VII (facial) and X (vagus) terminate in NS, also, but these are not involved in pressure sensations from the palate (Diamond, et al., 1985, Nolte, 2002). 1.7.2 WHICH RAPHE AND WHICH RETICULAR NUCLEUS?
A slice of the rostral (upper) medulla area containing NS, together with RaRN components, will be described. As shown In the simplified slice of Figure 6, the bilateral locations of the NS, lateral reticular nucleus (LRN), the reticular gigantocellularis nucleus (GC) and the raphe magnus (RaM) all share space horizontally within the reticular formation (RF) at the level of the middle NS. RF is indicated by the grey area in the slice. Referring to a previous figure, Figure 3, RF traverses the brainstem vertically in twin sections bilaterally, whose horizontal cross section is quite variable (unlike that shown in Figure 3). RF is an incredibly complex net of neuronal connections traversing vertically and horizontally to coordinate sleep-awake states, visceral functions, blood pressure, temperature control, movement of spinal and cerebellar muscular control and pain modulation, all of which are mediated by their own diffuse nuclei with uncertain boundaries.
As seen in Figure 6, the relevant nuclei within this level of the reticular formation (RF) are found in two zones: the lateral zone containing (LRN) and the medial zone containing RaM and GC. LRN and GC extend vertically into the pons area and LRN is primarily concerned with cranial nerve reflexes and visceral functions, while GC is associated with the hypoglossal nucleus involved in motor function. The intimate association between NS and RF is well documented (Diamond et al, 1985) as is that between the RaM and RF. It is assumed that these associations include LRN. One notable fact is that all efferent fibers from LRN are thought to serve the cerebellum, which sends afferents back to LRN (Nolte, 2002, Wikipedia).
This exchange of fibers is found in other raphe and reticular nuclei as well (Gerrits et al, 1985). The implication is that storage of sensory impulses involves a cerebellar nucleus, as will be discussed. Thus, a tentative identity of the reticular and raphe nuclei for the RaRN model will be those shown in Figure 6, LRN and RaM, with the likely assumption that all relevant connections are in place within the slice. The slice in Fig. 6 is shown in two conditions: without hallucinogens, or with LSD or EH (the endogenous hallucinogen), each of which have with coding, red or blue, to signify active or inactive states, respectively. In Figure 8a,b and c below, these will be presented to show impulse flow for three conditions to and from memory storage and the cerebral cortex.
1.7.3 THE ASCENT OF PAIN
1.7.4 The Emerging Fetus
Descriptions of pathways for the ascent of pain from NS to the sensory cortex involve essentially two different individuals, the fetus and the adult, for which the state of CNS maturity is quite different. However, the relevant pathways for the kind of pain (pressure) in M’s case are ancient on the phylogenic scale and present in both the fetus and the adult. More discussion of this difference can be found by clicking on the link, Fetal Ascent.
Pain or pressure impulses from the palate to the cerebral sensory cortex (Figure 7) travel first to the Nucleus solitarius (NS) and directly to the ventral posterior medial nucleus (VPM) within the left thalamus (top left of figure). VPM is dedicated to sending “affective” (hurt) sensory information directly to the SII sensory cortex (Figure 7, top right in red). Closely related pain of a different kind is relayed from the adjacent lateral medial posterior nucleus (LPM) of the thalamus to the S I cortex (blue) just posterior to the large horizontal sulcus, a crevasse separating visually the frontal and parietal lobes.
S I contains the homunculus at Broadman’s areas1,2 and 3 of the somatosensory cortex of the parietal lobe (Kandel et al, 2007). This “discriminative” pain locates the painful area (the palate in M’s case) and is carried by pathways much younger on the evolutionary scale. NS ascending fibers go directly to both VPM and LPM via the cerebral peduncle (a cable of fibers in the dorsal brainstem) and thence to the SII cortex via the internal capsule (another band of axon cables). Thus, this sensory traffic doesn’t involve synapses with the reticular formation (Nolte, 2002; Warner, 2001; Haines, 2004; Diamond et al., 1985). Because of this autonomy, pain or pressure impulses entering the NS are felt immediately, regardless of internal state of brainstem nuclei (to be discussed).1.75 The Thalamic Gate
Although the ascent of impulses from the thalamus VPM to SII is direct, it is modified in the thalamus. In addition to the fifteen thalamic relay nuclei on each side that are each dedicated to a specialized region of the cerebral cortex, there are seven intralaminar nuclei, which are not (Diamond et al, 1985; Nolte, 2002). One of these, the thalamic reticular nucleus (TRN) (not to be confused with the brainstem reticular nuclei) is a sheath that covers most of the thalamus to communicate with each relay nucleus, e.g., VPM. TRN contains a protective “gate” containing inhibitory neurons that regulate the volley of impulse traffic to and from VPM and the somatic cortex (Figure 8, below). Collateral fibers originating from the VPM-to-cortex fibers facilitate the ability of these TRN neurons to inhibit thalamocortical impulse flow by GABAergic inhibition in a system of positive feedback (Yen and Shaw, 2003). Returning fibers from the cortex also have collaterals that facilitate TRN neurons in the same way. As a result, the “gate” for thalamocortical traffic is not fully open and the intensity and reverberation of pain or pressure by the cortex is reduced. As one would suspect there is another TRN input that does the reverse, as described below.
Notably, 5-HT2a receptors reside in the thalamus and any hallucinogenic ligand would affect the precise functional organization for interactions between its relay nuclei and TRN to alter perception and cognition (Nichols, 2004 pp.163-65). The brevity and relatively minimal corresponding effect in M’s LSD session could be explained in part by the low dose, presumably insufficient to reach the threshold for these thalamic receptors. Another factor enhancing the clarity of M’s memory recall is the use of scopolamine in his birth, to be detailed below.
1.76 THE ADULT
While collateral potentiation of the thalamic reticular nucleus (TRN) reduces VPM-to-cortical impulse flow from below (the NS), another mechanism exists for restoring full flow by inhibiting TRN. As shown in Figure 8 TRN inhibition occurs from collaterals of midbrain fibers ascending from brainstem reticular nuclei via the midbrain at the top of the brainstem.
This brings up two points In the development of the proposed model: The impulses released from a brainstem memory substrate (by raphe inhibition) will arrive at the sensory cortex in full force, since these impulses inhibit the ability of TRN for attenuation. Accordingly, the ascent of stored impulses from M’s brainstem (on LSD) takes a different route and quality, vis-à-vis the newborn. For the newborn the ascent is from the palate to NS and directly to VPM. (Another route exists when EH is secreted at birth, from NS to storage in the cerebellum via the active LRN). This would also be the case for the adult on receiving a painful insult. However, for the adult, having a traumatic memory recall, the impulses ascend from a reticular nucleus and their intensity into the cortical region is not diminished. The diagram in Figure 7 illustrates the TRN control of VPM-cortex flow when TRN activity is both facilitated and inhibited.1.7.7x THE “DESCENT”: THE PATHS FOR STORAGE AND RELEASE OF IMPULSES TO AND FROM THE MEMORY SUBSTRATE
The crux of the main hypothesis lies within the direction of brainstem fibers from NS to storage. It is referred to as “descent”, although it’s actually a small oblique lateral path to a deep cerebellar nucleus. Here, communication of descending impulses between NS and memory storage requires the intimate connection of NS descending fibers with the (putative) lateral reticular nucleus, postulated to be sensitive to raphe magnus activity. As already mentioned, the NS has been found to be intimately associated with the pontomedullary reticular formation (Diamond et al. 1985) and by putative association, with LRN. With persistent RaM activity, LRN acts normally as a blocking nucleus. The proposal is that normal raphe repression of this LRN would prevent the transfer of sensory impulses to storage from NS (What is meant by “storage” will be discussed below). Conversely, suppression of the raphe nuclei would dis-inhibit LRN and allow impulse flow in either direction, i.e., from NS to storage and from storage to the thalamocortical areas. Thus, this model provides an anatomical basis for both the implantation (encryption) and retrieval of the sensory imprint, together with a normal condition, in which a physical insult is felt, but not stored. These conditions are illustrated in Figures 8a, b and c, next.
1.7.8 THREE PHARMACOLOGICAL CONDITIONS
Figures 9a,b and c illustrate these paths of impulse flow to cerebral and cerebellar areas with respect to sensory input, storage and recall. The paths are drawn with directional arrows to show the polarity of impulse traffic. In Figure 9a the condition is sketched for the normal case, where a physical insult is felt, but not stored as hidden memory within the brainstem.
Here, the normally active RaM (red) suppresses the LRN neuron (blue) during sensory input, blocking the route between NS and storage in the cerebellum at the top of the figure. As shown also in Figure 8 the impulses ascend into the thalamic VPM nucleus, activating the TRN to reduce impulse intensity into S II or the “affective” cortex. This would be the normal state, owing to the constant spontaneous firing of the serotoninergic neurons of raphe magnus (RaM) known to be inhibited by LSD (Briggs, 1977). In this case a physical insult wouldn’t be stored as a memory to affect future central activity in some unconscious manner. Storage requires attenuation of the RaM serotoninergic neurons, normally made chronically active by their somatodendritic autoreceptors (Nichols, 2004). In the case of M’s LSD recall (Figure 9b), impulses from the sensory memory stored in the cerebellum at birth are allowed to flow from a deep cerebellar nucleus, e.g., the interpositus, through (now active) LRN to NS and to the thalamocortical area to produce his subjective experience of palate pressure. Here, the palate sensory area is not operative (blue), LSD inhibits the RaM nucleus (blue), the LRN neurons are active (red) and impulse flow to the cerebellum to LRN to NS to the thalamic VPM nucleus takes place. In this figure the sensory nucleus, NS, is shown as a relay point for the ascent of storage impulses directly to the thalamus VPM as they escape from cerebellar storage. Any alternative route might not be expected to occur outside the brainstem in response to LSD.
Figure 9c illustrates the condition of receiving the palate pressure at the time of birth. Here, the sensory insult goes directly to S II from NS as in Fig. 8a, but it also travels to the cerebellum from NS via LRN, now active in response to inhibition of RaM. As already discussed, the loss of raphe activity could reflect the well-known inhibitory effects of the GABA system that is known to be involved in birth from research on rat parturition (Lin et al, 1995, 1998). However, the notion that this inhibitor is a hallucinogen is based on the action of LSD in M’s case and the similarities of LSD and DMT with respect to their equally strong binding to the 5-HT1a receptor (McKenna et al 1990). According to the postulated bidirectional or “on-off” arrangement, at birth the LRN was active. Otherwise, according to the model, the palate sensations would not have been stored, in accordance with the notion that the pharmacological conditions of the adult and the fetus were the same. It is implied that the birth condition would require the presence of an endogenous raphe inhibitor that acts in the same manner as LSD did with M’s first experience.
Next: The page on the role of REM sleep is suggested, accessed by the button at top. For the second of the two LSD effects, the link, 2.1 will take you there. Otherwise, the proposal of hallucinogens in normal birth may be accessed now with the link, 1.12.
