Information

What is the mechanism by which Melatonin increases dream vividness and intensity in humans?

What is the mechanism by which Melatonin increases dream vividness and intensity in humans?


We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

I'm looking at the wikipedia article on Melatonin and noticed that it mentions vivid dreaming caused by melatonin. I have the "Melatonin and the Biological clock" pamphlet referenced in the article, and it does not go into too much detail of how vivid dreaming is happening.

I've personally experienced vivid dreaming side effects of melatonin today - dream after dream of profound intensity, but completely unrelated content. This makes me interested - how does melatonin influence the intensity of dreaming in humans? Is it by interaction with Serotonin? Or does it get metabolized into something psychoactive?


Differences between nighttime REM and NREM dreams are well-established but only rarely are daytime REM and NREM nap dreams compared with each other or with daydreams. Fifty-one participants took daytime naps (with REM or NREM awakenings) and provided both waking daydream and nap dream reports. They also provided ratings of their bizarreness, sensory experience, and emotion intensity. Recall rates for REM (96%) and NREM (89%) naps were elevated compared to typical recall rates for nighttime dreams (80% and 43% respectively), suggesting an enhanced circadian influence. All attribute ratings were higher for REM than for NREM dreams, replicating findings for nighttime dreams. Compared with daydreams, NREM dreams had lower ratings for emotional intensity and sensory experience while REM dreams had higher ratings for bizarreness and sensory experience. Results support using daytime naps in dream research and suggest that there occurs selective enhancement and inhibition of specific dream attributes by REM, NREM and waking state mechanisms.

Research was conducted at the Dream & Nightmare Laboratory, Center for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal and was funded by grants to T. Nielsen from the Natural Sciences and Engineering Research Council of Canada (#312277) and the Canadian Institutes of Health Research (MOP-115125). These funding agencies had no role in study design in the collection, analysis and interpretation of data in the writing of the report and in the decision to submit the article for publication.


Abstract

In mammals, a central circadian clock, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, tunes the innate circadian physiological rhythms to the ambient 24 h light–dark cycle to invigorate and optimize the internal temporal order. The SCN-activated, light-inhibited production of melatonin conveys the message of darkness to the clock and induces night-state physiological functions, for example, sleep/wake blood pressure and metabolism. Clinically meaningful effects of melatonin treatment have been demonstrated in placebo-controlled trials in humans, particularly in disorders associated with diminished or misaligned melatonin rhythms, for example, circadian rhythm-related sleep disorders, jet lag and shift work, insomnia in children with neurodevelopmental disorders, poor (non-restorative) sleep quality, non-dipping nocturnal blood pressure (nocturnal hypertension) and Alzheimer's disease (AD). The diminished production of melatonin at the very early stages of AD, the role of melatonin in the restorative value of sleep (perceived sleep quality) and its sleep-anticipating effects resulting in attenuated activation of certain brain networks are gaining a new perspective as the role of poor sleep quality in the build-up of β amyloid, particularly in the precuneus, is unravelled. As a result of the recently discovered relationship between circadian clock, sleep and neurodegeneration, new prospects of using melatonin for early intervention, to promote healthy physical and mental ageing, are of prime interest in view of the emerging link to the aetiology of Alzheimer's disease.

Linked Articles

This article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc

Abbreviations


Reader Interactions

Comments

That’s very interesting and would describe why some psychedelic visual images can linger for years (they may be normal functions but now we associate them with a drug).

I understand the connection you describe here but I’m wondering then why dreaming so seldom provides the “one with the cosmos” or the omnipotence of the psychedelic experience.

Besides my “I can fly” dreams earlier in my life, I’ve had no feelings of omnipotence or absolute perfection while dreaming, especially at my age now.

Is it because psychedelics act on the limbic system? And is dissociation in dreams what Freud refers to when he says that we are everyone in our dreams? All the players?

Dissociation with psychedelics is more obvious afterward.

That’s a really interesting article. Now here’s a question for you — do you think that the regular use of psychedelics would increase or lessen the vividness of the “hallucinations” you experience while dreaming?

Thanks for your comment and you ask some very good questions.

Large amounts of the psychedelic DMT are produced in the lungs practically at all times in our lives, and especially during heaving breathing, but I am also sure that many of us don’t have the same psychedelic type experienced while smoking DMT or during an Ayahuasca session. A lot of the explanation might be set and setting or even how the compounds are produced in the brain but the ultimate truth is we just don’t know.

From my own personal experience I have had very psychedelic like dreams where I have experienced everything one would experience during a drug induced experience. The only true difference would be that it was natural so my mind didn’t have the fears one has when they take a drug, and I wasn’t as fully lucid as I would be if I took the drug while being awake.

It would be interesting if I could find some more information of people have taken psychedelics and then have gone to sleep right away and how much different their dreams would be. I know of only one individual that done that and he said that his dreams were normal. Again great question.

I also want to highlight an article by Charles Tart in his classic Altered States of Consciousness titled “the High Dream: A new state of consciousness”, where he defines dreams that approximate psychedelic experience. He reports that they can follow a LSD-25 session or happen spontaneously.

I would never suggest using psychedelics in order to dream more often as they are not only illegal but also have little known studies done with them in reference to sleep due to their restricted control. I know that people who have used them have explained that their dreams have changed since they started using in that they are more psychedelic like and have more interesting characters.

i second that. that would be an interesting hermeneutic study, tho. my guess is that those who use psychedelics are in a subset of the population who value their creative insights, so they probably already have cool dreams. but taking the pill won’t make you chill.

DMT in the lungs. Intriguing. Breathing is connected to the emotional quality of experiences. Might breathing be affected in dream states by the presence of DMT? Could the presence of DMT be caused by the emotional content of the dream, or influence the emotional content?
I consider how breathing techniques themselves are used to affect the emotional experience – meditation, singing/acting, getting pumped. Might DMT be playing a role in altering the conscious state?

Karen great point and yes many people have suggested that the large amount of breathing work that people do during spiritual traditions is in support of this. Our brains are also very complicated and its very possible that dreams themselves are due to the brains release of a substance like DMT.

You said that you don’t have the fears someone would get from taking psychedelic drugs because your brain naturally produced the chemicals, but I have had horrific(and very odd)lucid nightmares and have just started experimenting again after a few years off. I am very apprehensive and am sure this is affecting my ability to stay conscious now, do you have any ideas on nightmare prevention as the thought of disembowelment or having my arm chopped off by a samarai warrior is quite a deterrent?

Liam, check out my post on dealing with lucid nightmares. it’s the last post in a series discussing lucid dreams and nightmares with some practical advice towards the end of the article.

taking a melatonin supplement at night is an excellent meditation aid, very easy to enter into hypnagogic state

however when returning to waking consciousness the condition of the mind is so drowsy that it is hard to rouse oneself to activity

seems that by entering that altered state the melatonin supplement really kicks something into gear intensely

i am doing experiments with it, very hopeful for it too

using melatonin got me off other drugs as i began to see the correlation between melatonin and vivid dream states and trance states

i call it ‘sleepy buddha’ because after taking melatonin at night (in a dim environment, lights seem to put it ‘on hold’ for a while) one feels drowsy but content, detached and dreamy, but as soon as one begins meditation there is a heightened lucidity vividly present and one dissolves into no-mind states easily

fortunately it seems that melatonin can’t be abused as a recreational drug – i.e., anyone taking it looking to trip while they are awake will probably get nothing more than intense drowsiness, but if they fall asleep they will have vivid dreams. i believe the real secret to melatonin lies in the meditative trance states, they are subtle variations on the natural states of dream mind and deep sleep mind already, but meditation ‘activates’ them.

email me for more info if you like

thanks Elusiivvvva for your melatonin report. I agree with you that it seems like a substance that will never be a “party” drug. There is the possibility of overdose on melatonin, but you have to really overdo it.

Elusiivvva its interesting that you say that melatonin is helping you experience the meditative state. I know that melatonin helps support sleep and drowsy states, but if Callaway is correct in his theory of DMT being produced during sleep stages when melatonin levels are highest then DMT is being produced when you are meditating. I think the possibility of DMT being produced at this time could help you get the same effects as other recreational drugs that give you trance effects since most rely on the same base chemicals.

Lee, look into Mantak Chia’s writings on ‘dark retreat’ meditation practices. He goes into the process that occurs in dark retreat and the functioning of the pineal gland, melatonin, dmt, etc.

Dark retreat is basically just to sit in total darkness with open eyes for an extended period of time. Sometimes hours, sometimes days, sometimes weeks, and so on. In the Tibetan Buddhist tradition it is held in very high esteem and there are many legends of the unusual experiences had by yogis in it.

I have experimented with this practice also and can confirm that in response to the total darkness (since even subtle lights seem to exert a powerful influence on the brain in what would otherwise be a totally dark space), the brain is flooded with melatonin, which causes the post-session drowsiness and mental calm etc. I have also witnessed the beginning stages of something which I can only describe tentatively as a “dying” process. I had been engaged in the practice for hours (staring into darkness, emptying the mind) and the body entered such a deeply relaxed state that the breath became very slow and labored, as if driven by a force beyond myself (possessed by some energy), the beginnings of ‘kundalini’ began around my lower back area, and my mind seemed to be disappearing entirely. The vacuity flooding my senses was possessing my being, I was disappearing as a mind totally. At the time, it terrified me and I struggled to stop the process, fearing that I had activated some sort of ‘death program’ in the body and it was shutting down for good!

I have a different perspective on it now of course and am planning on engaging in the practice again, this time taking the melatonin supplements as well to see what happens. It seemed to be the beginning of a true shamanic state, without the use of any drugs, and different from other meditative states of absorption in its intensity and all the physical symptoms.

If DMT is released during sleep or other trance states and that is the reason for very lucid visions and such then I can also confirm without a doubt that dark retreat also activates it fairly quickly (at least in this case). I’ve had several vivid visions, “OOBE’s” and such things in dark retreat due to the lack of any sort of visual stimulation. It is similar to John Lilly’s isolation tank experiences, even following the same stages he writes about, just without the water tank. The same discomfort arises after a while when no external stimulation arises, and the inner mind basically throws open its doors for you to enter in. With my meditation practice, though, I would consider engaging in those dream worlds to be fascinating but besides the point, not quite as deep/transformative as the death like samadhi states.

Also look into Osho’s “my awakening” story on realization.org. It is known that around age 21 he also practiced dark retreat nightly, and his ‘enlightenment’ experience recorded in that story seems like a DMT thing. He mentions that he fell into a deep samadhi-like sleep and when he awoke he felt immersed in blissful energy, the walls were melting – he was tripping, but without taking any drug externally. I believe that this was entirely due to his dark retreat meditations and the melatonin building up in his system (and converting to DMT).

Interesting suppositions on dreaming and the pyschedelic connection…. the bit on DMT being found in lungs was surprising to me. I was given LSD-25 back in the time it was still legal in my country [a long, long time ago]. Found it very strong and quite scary, although some effects were fascinating and indescribable.


Melatonin Production and Physiological Actions

What Is the Pathway of Melatonin Production?

In mammals, the biosynthesis of melatonin starts with the conversion of tryptophan to l-5-hydroxytryptophan, which is converted to serotonin [5-hydroxytryptamine(5-HT)] by the aromatic l-amino acid decarboxylase (AADC). Serotonin is acetylated by the phosphorylated arylalkylamine N-acetyltransferase (P-AANAT), forming N-acetylserotonin (NAS), which is converted to melatonin by N-acetylserotonin O-methyltransferase (ASMT). The melatonin pineal daily rhythm is determined by the conversion of 5HT to NAS under sympathetic control ( Figure 2 ). Environmental light modifies the structure of melanopsin in the retinal ganglion cells triggering glutamate excitation at the retino-hypothalamic tract that projects to the SCN. The SCN inhibits the hypothalamic paraventricular nucleus (PVN) via GABAergic projection. In the absence of light, the PVN activates the ganglion cervical nuclei (via the intermediolateral column of the medulla) activating noradrenergic fibers that innervate the pineal gland, ultimately releasing the co-transmitters noradrenaline and ATP (41). Consequently, the production of melatonin depends on the integrity of the brain monoaminergic system (2). Beta-1 adrenergic receptor activation leads to increase in cAMP and activation of protein kinase A, which promotes the phosphorylation of the cyclic AMP regulating element (CREB) and the phosphorylation of AANAT (P-AANAT). Phospho-CREB induces the transcription of the gene that codifies AANAT (the native form of the enzyme), which is immediately degraded by the proteasome. In nocturnal animals both the control of transcription and activation of AANAT plays an important role in melatonin synthesis, while in diurnal animals the transcription of the gene is constitutive (1) thus, nocturnal melatonin surge is delayed in nocturnal rodents when compared to humans. Circulating melatonin levels in the bloodstream accurately reflects pineal synthesis (2). At dark-night the pineal melatonin plasma levels show a 10�-fold increase in normally entrained individuals. When light is turned on in the middle of the dark night, the pineal melatonin synthesis stops, and melatonin concentration in the blood is abruptly reduced due to liver metabolization (first-pass effect). In the liver, melatonin is metabolized to 6-sulfatoxymelatonin (aMT6s), excreted in the urine, which is well-correlated with plasma melatonin ( Figure 2 ) (42).

The canonical pathway of pineal melatonin production. The suprachiasmatic nucleus (SCN) receives environmental photic information collected by intrinsically photosensitive ganglion cells (ipRGC) in the retina. The ipRGCs express the photopigment melanopsin, which transduces light wavelengths into neural input through the retinohypothalamic tract (RHT) to the SCN. The SCN constitutively inhibits the hypothalamic paraventricular nucleus (PVN) via GABAergic projection. In the absence of light, the PVN activates the ganglion cervical nuclei (SCG, via the intermediolateral column of the medulla) triggering noradrenergic fibers that innervate the pineal gland (PG), ultimately releasing the co-transmitters noradrenaline and ATP. This sympathetic stimulus triggers the action of arylalkylamine N-acetyltransferase (AANAT) converting serotonin (5TH) into N-acetylserotonin (NAS) within the pinealocyte. With the constitutive action of N-acetylserotonin O-methyltransferase (ASMT), NAS is then converted to melatonin and immediately released into the cerebrospinal fluid and bloodstream. Through first-pass metabolism in the liver, melatonin is converted to 6-sulfatoxymelatonin (aMT6s), which is then excreted in the urine.

How Is Melatonin Production Regulated?

The pineal gland is a circumventricular organ that monitors the level of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) in the cerebrospinal fluid (CSF) and peripheral circulation. In pinealocytes, the activation of the NF㮫 pathway by toll-like receptors and TNFRs inhibits AANAT-gene transcription both in diurnal and nocturnal animals. Cortisol or corticosterone at concentrations compatible with arousal (but not the ones found in models of chronic unpredictable mild stress) potentiate melatonin synthesis, while concentrations compatible with immune suppression blocks it. In immune-competent cells PAMPs and DAMPs promote the synthesis of melatonin by activating the transcription of the gene that codifies AANAT. This process is also dependent on the binding of NFkB dimers to the gene promoter, but it is not an immediate effect. Activation of PAMPs or DAMPs receptors promote the nuclear translocation of the NFkB dimer (p50/p65) that leads to the synthesis of the subunit (cRel) necessary for activating AANAT transcription. The induction of melatonin synthesis in rodents and human macrophages by the transcription factor is a hallmark in inflammatory responses and inflammation (43�). The fact that stressful conditions increase extra-pineal melatonin synthesis independently of environmental light strongly suggests that the amplitude of daily melatonin rhythm, classically attributed to reduction of nocturnal melatonin synthesis, may also result from an increase of the output from extra-pineal sources (1).

During the mounting of an innate immune response melatonin plays various roles: the reduction of nocturnal melatonin leads to the mobilization of leukocytes from the bone marrow to the blood, and from the blood to the site of lesion the synthesis of melatonin by macrophages/microglia increases its phagocytic ability and reduces the oxidative stress participating in the recovery phase of the inflammatory response (1). The return of macrophages/microglia/phagocytes counts to baseline requires the return of mediators' levels active at the recovery phase, including melatonin, to basal values. When the recovery from the acute inflammatory response is mediated only by pineal activity return to baseline, without restoration of macrophage melatonin synthesis to baseline, the result is a resilient state (low-inflammatory grade).

Over the past decades, studies reported neuroinflammatory responses in a series of neurodegenerative and psychiatric disorders. Intense research has been undertaken to determine the critical elements of such responses and putative therapies for their suppression. Some reports associate MDD to increased levels of cytokines including TNFα, IL-6, and IL-1β, as well as a reduction in complement C3 (47�). Increased immune-inflammation, with high oxidative and nitrosative stress leading to changes in neuronal regulating tryptophan catabolites (TRYCATs) and mitochondrial dysfunction, have been documented in the progressive course of MDD (50, 51). In animal models, melatonin treatment significantly abolished the effects of LPS and reduced NF-㮫 in the cortex and the hippocampus, both effects resulting in an improvement of depressive-like behaviors (52). These results point to the possibility of an 𠇊ntidepressant effect” of melatonin via the interplay with the immune system. Furthermore, as described above, cortisol functioning and its circadian fluctuation is essential for the adequate melatonin surge. Blunted cortisol rhythms (i.e., lower morning cortisol peak and higher daytime values) have been demonstrated in association with depressive symptoms in humans (49, 53, 54).

How Does Melatonin Exert Its Physiological Actions?

Melatonin effects triggered by a large range of concentrations (pM to mM) are mediated by mechanisms of action with different grades of sensitivity. The effects of exogenous vs. endogenous melatonin, as well as the concentration reached by intracrine/autocrine, paracrine and hormonal sources, depend on the melatonin bioavailability and the mechanisms that mediate each production source. In a concentration range compatible with the nocturnal surge (pM to nM), melatonin orchestrates a plethora of physiological functions by activating GPCRs receptors (MT1 and MT2) localized in plasmatic, nuclei and mitochondrial membranes. At much higher concentrations, melatonin may act as an electron donor, promoting a receptor free non-specific antioxidant response (55). Other non-receptor mediated actions include the regulation of clock genes expression (by directly inhibiting the proteasome), and inhibition of the ubiquitin–proteasome system that ultimately controls protein degradation.

Melatonin receptors MT1 and MT2 couple to Gi/o and beta-arrestins and depending on the context also couple to Gq (55). The second messenger immediate responses result in an increase/decrease of cAMP or increase in intracellular or intramitochondrial free calcium (56). The internalization of the receptors upon stimulation leads to the activation of ERK pathways, which modulate intranuclear responses. MT1/MT2 receptors form heterodimers with pharmacological properties different from MT2 homodimers. The heterodimerization of the MT1 receptor with the orphan receptor GPR50 impairs its interaction with melatonin (57). Thus, another source of variability of melatonin response are the changes in the expression and the dimerization of melatonin receptors induced by pathophysiological and pathological states.

Pineal melatonin exerts a wide range of physiological actions due to its release into the cerebrospinal fluid (CSF) and bloodstream. As a hormone that gains the bloodstream at night in the dark, melatonin is an internal temporal cue that has immediate interactions with its molecular effectors as well as prospective effects, since it primes physiological responses that will take place hours after its peak. The duration, timing, and cyclic-nature of pineal melatonin production, as well as its seasonal variation according to photoperiod changes, contribute to the temporal organization of physiological phenomena into circadian and circannual timescales (58). Finally, transgenerational effects have been described, as maternal melatonin reaches the fetus via placenta and constitutes the only fetal source of intrauterine melatonin. As previously stated, extra-pineal melatonin shows immediate effects in the cells and tissues where it is produced, and the current knowledge does not support any eigen-zeitgeber action (i.e., being an internal temporal cue) or seasonal effect resulting from these sources. A detailed review on the physiological actions of melatonin was composed by Cipolla-Neto and Amaral (59).


What does it mean when we dream?

Dreams are stories and images that our minds create while we sleep. They can be entertaining, fun, romantic, disturbing, frightening, and sometimes bizarre.

They are an enduring source of mystery for scientists and psychological doctors. Why do dreams occur? What causes them? Can we control them? What do they mean?

This article will explore the current theories, causes, and applications of dreaming.


Dreams: Do they represent our unconsious desires?

There are several theories about why we dream. Are dreams merely part of the sleep cycle, or do they serve some other purpose?

Possible explanations include:

  • representing unconscious desires and wishes
  • interpreting random signals from the brain and body during sleep
  • consolidating and processing information gathered during the day
  • working as a form of psychotherapy

From evidence and new research methodologies, researchers have speculated that dreaming serves the following functions:

  • offline memory reprocessing, in which the brain consolidates learning and memory tasks and supports and records waking consciousness
  • preparing for possible future threats
  • cognitive simulation of real life experiences, as dreaming is a subsystem of the waking default network, the part of the mind active during daydreaming
  • helping develop cognitive capabilities
  • reflecting unconscious mental function in a psychoanalytic way
  • a unique state of consciousness that incorporates experience of the present, processing of the past, and preparation for the future
  • a psychological space where overwhelming, contradictory, or highly complex notions can be brought together by the dreaming ego, notions that would be unsettling while awake, serving the need for psychological balance and equilibrium

Much that remains unknown about dreams. They are by nature difficult to study in a laboratory, but technology and new research techniques may help improve our understanding of dreams.

Phases of sleep


Dreams most likely happen during REM sleep.

There are five phases of sleep in a sleep cycle:

Stage 1: Light sleep, slow eye movement, and reduced muscle activity. This stage forms 4 to 5 percent of total sleep.

Stage 2: Eye movement stops and brain waves become slower, with occasional bursts of rapid waves called sleep spindles. This stage forms 45 to 55 percent of total sleep.

Stage 3: Extremely slow brain waves called delta waves begin to appear, interspersed with smaller, faster waves. This accounts for 4 to 6 percent of total sleep.

Stage 4: The brain produces delta waves almost exclusively. It is difficult to wake someone during stages 3 and 4, which together are called “deep sleep.” There is no eye movement or muscle activity. People awakened while in deep sleep do not adjust immediately and often feel disoriented for several minutes after waking up. This forms 12 to 15 percent of total sleep.

Stage 5: This stage is known as rapid eye movement (REM). Breathing becomes more rapid, irregular, and shallow, eyes jerk rapidly in various directions, and limb muscles become temporarily paralyzed. Heart rate increases, blood pressure rises, and males develop penile erections. When people awaken during REM sleep, they often describe bizarre and illogical tales. These are dreams. This stage accounts for 20 to 25 percent of total sleep time.

Neuroscience offers explanations linked to the rapid eye movement (REM) phase of sleep as a likely candidate for the cause of dreaming.

Dreams are a universal human experience that can be described as a state of consciousness characterized by sensory, cognitive and emotional occurrences during sleep.

The dreamer has reduced control over the content, visual images and activation of the memory.

There is no cognitive state that has been as extensively studied and yet as frequently misunderstood as dreaming.

There are significant differences between the neuroscientific and psychoanalytic approaches to dream analysis.

Neuroscientists are interested in the structures involved in dream production, dream organization, and narratability. However, psychoanalysis concentrates on the meaning of dreams and placing them in the context of relationships in the history of the dreamer.

Reports of dreams tend to be full of emotional and vivid experiences that contain themes, concerns, dream figures, and objects that correspond closely to waking life.

These elements create a novel “reality” out of seemingly nothing, producing an experience with a lifelike timeframe and connections.

Nightmares

Nightmares are distressing dreams that cause the dreamer to feel a number of disturbing emotions. Common reactions to a nightmare include fear and anxiety.

They can occur in both adults and children, and causes include:

Lucid dreams

Lucid dreaming is the dreamer is aware that they are dreaming. They may have some control over their dream.

This measure of control can vary between lucid dreams. They often occur in the middle of a regular dream when the sleeping person realizes suddenly that they are dreaming.

Some people experience lucid dreaming at random, while others have reported being able to increase their capacity to control their dreams.

What goes through our minds just before we fall asleep could affect the content of our dreams.

For example, during exam time, students may dream about course content. People in a relationship may dream of their partner. Web developers may see programming code.

These circumstantial observations suggest that elements from the everyday re-emerge in dream-like imagery during the transition from wakefulness to sleep.

Characters

Studies have examined the “characters” that appear in dream reports and how they the dreamer identifies them.

  • Forty-eight percent of characters represented a named person known to the dreamer.
  • Thirty-five percent of characters were identified by their social role (for example, policeman) or relationship to dreamer (such as a friend).
  • Sixteen percent were not recognized
  • Thirty-two percent were identified by appearance
  • Twenty-one percent were identified by behavior
  • Forty-five percent were identified by face
  • Forty-four percent were identified by “just knowing”

Elements of bizarreness were reported in 14 percent of named and generic characters.

Another study investigated the relationship between dream emotion and dream character identification.

Affection and joy were commonly associated with known characters and were used to identify them even when these emotional attributes were inconsistent with those of the waking state.

The findings suggest that the dorsolateral prefrontal cortex, associated with short-term memory, is less active in the dreaming brain than during waking life, while the paleocortical and subcortical limbic areas are more active.

Memories

The concept of ‘repression’ dates back to Freud. Freud maintained that undesirable memories could become suppressed in the mind. Dreams ease repression by allowing these memories to be reinstated.

A study showed that sleep does not help people forget unwanted memories. Instead, REM sleep might even counteract the voluntary suppression of memories, making them more accessible for retrieval.

Two types of temporal effects characterize the incorporation of memories into dreams:

  • the day-residue effect, involving immediate incorporations of events from the preceding day
  • the dream-lag effect, involving incorporations delayed by about a week
  • processing memories into dream incorporation takes a cycle of around 7 days
  • these processes help further the functions of socio-emotional adaptation and memory consolidation

Dream lag

Dream-lag is when the images, experiences, or people that emerge in dreams are images, experiences, or people you have seen recently, perhaps the previous day or a week before.

The idea is that certain types of experiences take a week to become encoded into long-term memory, and some of the images from the consolidation process will appear in a dream.

Events experienced while awake are said to feature in 1 to 2 percent of dream reports, although 65 percent of dream reports reflect aspects of recent waking life experiences.

The dream-lag effect has been reported in dreams that occur at the REM stage but not those that occur at stage 2.

Memory types and dreaming

Two types of memory can form the basis of a dream.

  • autobiographical memories, or long-lasting memories about the self
  • episodic memories, which are memories about specific episodes or events

A study exploring different types of memory within dream content among 32 participants found the following:

  • One dream (0.5 percent) contained an episodic memory.
  • Most dreams in the study (80 percent) contained low to moderate incorporations of autobiographical memory features.

Researchers suggest that memories of personal experiences are experienced fragmentarily and selectively during dreaming. The purpose may be to integrate these memories into the long-lasting autobiographical memory.

A hypothesis stating that dreams reflect waking-life experiences is supported by studies investigating the dreams of psychiatric patients and patients with sleep disorders. In short, their daytime symptoms and problems are reflected in their dreams.

In 1900, Freud described a category of dreams known as “biographical dreams.” These reflect the historical experience of being an infant without the typical defensive function. Many authors agree that some traumatic dreams perform a function of recovery.

One paper hypothesizes that the main aspect of traumatic dreams is to communicate an experience that the dreamer has in the dream but does not understand. This can help an individual reconstruct and come to terms with past trauma.

Themes

The themes of dreams can be linked to the suppression of unwanted thoughts and, as a result, an increased occurrence of that suppressed thought in dreams.

Fifteen good sleepers were asked to suppress an unwanted thought 5 minutes prior to sleep.

The results demonstrate that there were increased dreams about the unwanted thought and a tendency to have more distressing dreams. They also imply that thought suppression may lead to significantly increased mental disorder symptoms.

Research has indicated that external stimuli presented during sleep can affect the emotional content of dreams.

For example, the positively-toned stimulus of roses in one study yielded more positively themed dreams, whereas the negative stimulus of rotten eggs was followed by more negatively themed dreams.

Typical dreams are defined as dreams similar to those reported by a high percentage of dreamers.

Up to now, the frequencies of typical dream themes have been studied with questionnaires. These have indicated that a rank order of 55 typical dream themes has been stable over different sample populations.


Some themes are familiar to many people, such as flying, falling, and arriving late.

The 55 themes identified are:

  • school, teachers, and studying
  • being chased or pursued
  • sexual experiences
  • falling
  • arriving too late
  • a living person being dead
  • a person now dead being alive
  • flying or soaring through the air
  • failing an examination
  • being on the verge of falling
  • being frozen with fright
  • being physically attacked
  • being nude
  • eating delicious food
  • swimming
  • being locked up
  • insects or spiders
  • being killed
  • losing teeth
  • being tied up, restrained, or unable to move
  • being inappropriately dressed
  • being a child again
  • trying to complete a task successfully
  • being unable to find toilet, or embarrassment about losing one
  • discovering a new room at home
  • having superior knowledge or mental ability
  • losing control of a vehicle
  • fire
  • wild, violent beasts
  • seeing a face very close to you
  • snakes
  • having magical powers
  • vividly sensing, but not necessarily seeing or hearing, a presence in the room
  • finding money
  • floods or tidal waves
  • killing someone
  • seeing yourself as dead
  • being half-awake and paralyzed in bed
  • people behaving in a menacing way
  • seeing yourself in a mirror
  • being a member of the opposite sex
  • being smothered, unable to breathe
  • encountering God in some form
  • seeing a flying object crash
  • earthquakes
  • seeing an angel
  • part animal, part human creatures
  • tornadoes or strong winds
  • being at the movie
  • seeing extra-terrestrials
  • traveling to another planet
  • being an animal
  • seeing a UFO
  • someone having an abortion
  • being an object

Some dream themes appear to change over time.

For example, from 1956 to 2000, there was an increase in the percentage of people who reported flying in dreams. This could reflect the increase in air travel.

What do they mean?

Relationships: Some have hypothesized that one cluster of typical dreams, including being an object in danger, falling, or being chased, is related to interpersonal conflicts.

Sexual concepts: Another cluster that includes flying, sexual experiences, finding money, and eating delicious food is associated with libidinal and sexual motivations.

Fear of embarrassment: A third group, containing dreams that involve being nude, failing an examination, arriving too late, losing teeth, and being inappropriately dressed, is associated with social concerns and a fear of embarrassment.

Brain activity and dream types

In neuroimaging studies of brain activity during REM sleep, scientists found that the distribution of brain activity might also be linked to specific dream features.

Several bizarre features of normal dreams have similarities with well-known neuropsychological syndromes that occur after brain damage, such as delusional misidentifications for faces and places.

Dreams and the senses

Dreams were evaluated in people experiencing different types of headache. Results showed people with migraine had increased frequency of dreams involving taste and smell.

This may suggest that the role of some cerebral structures, such as amygdala and hypothalamus, are involved in migraine mechanisms as well as in the biology of sleep and dreaming.

Music in dreams is rarely studied in scientific literature. However, in a study of 35 professional musicians and 30 non-musicians, the musicians experienced twice as many dreams featuring music, when compared with non-musicians.

Musical dream frequency was related to the age of commencement of musical instruction but not to the daily load of musical activity. Nearly half of the recalled music was non-standard, suggesting that original music can be created in dreams.

It has been shown that realistic, localized painful sensations can be experienced in dreams, either through direct incorporation or from memories of pain. However, the frequency of pain dreams in healthy subjects is low.

In one study, 28 non-ventilated burn victims were interviewed for 5 consecutive mornings during their first week of hospitalization.

  • Thirty-nine percent of people reported pain dreams.
  • Of those experiencing pain dreams, 30 percent of their total dreams were pain-related.
  • Patients with pain dreams showed evidence of reduced sleep, more nightmares, higher intake of anxiolytic medication, and higher scores on the Impact of Event Scale.
  • Patients with pain dreams also had a tendency to report more intense pain during therapeutic procedures.

More than half did not report pain dreams. However, these results could suggest that pain dreams occur at a greater frequency in populations currently experiencing pain than in normal volunteers.

Self-awareness

One study has linked frontotemporal gamma EEG activity to conscious awareness in dreams.

The study found that current stimulation in the lower gamma band during REM sleep influences on-going brain activity and induces self-reflective awareness in dreams.

Researchers concluded that higher order consciousness is related to oscillations around 25 and 40 Hz.

Relationships

Recent research has demonstrated parallels between styles of romantic attachment and general dream content.

Assessment results from 61 student participants in committed dating relationships of six months duration or longer revealed a significant association between relationship-specific attachment security and the degree to which dreams about romantic partners followed.

The findings illuminate our understanding of mental representations with regards to specific attachment figures.

Death in dreams

Researchers compared the dream content of different groups of people in a psychiatric facility. Participants in one group had been admitted after attempting to take their own lives.

Their dreams of this group were compared with those of three control groups in the facility who had experienced:

    and thoughts about suicide
  • depression without thinking about suicide
  • carrying out a violent act without suicide

Those who had considered or attempted suicide or carried out violence had were more likely to have dreams with content relating to death and destructive violence. One factor affecting this was the severity of an individual’s depression.

Left and right side of the brain

The right and left hemispheres of the brain seem to contribute in different ways to a dream formation.

Researchers of one study concluded that the left hemisphere seems to provide dream origin while the right hemisphere provides dream vividness, figurativeness and affective activation level.

A study of adolescents aged 10 to 17 years found that those who were left-handed were more likely to experience lucid dreams and to remember dreams within other dreams.

Studies of brain activity suggest that most people over the age of 10 years dream between 4 and 6 times each night, but some people rarely remember dreaming.

It is often said that 5 minutes after a dream, people have forgotten 50 percent of its content, increasing to 90 percent another 5 minutes later.

Most dreams are entirely forgotten by the time someone wakes up, but it is not known precisely why dreams are so hard to remember.

Steps that may help improve dream recall, include:

  • waking up naturally and not with an alarm
  • focusing on the dream as much as possible upon waking
  • writing down as much about the dream as possible upon waking
  • making recording dreams a routine

Who remembers their dreams?

There are factors that can potentially influence who remembers their dreams, how much of the dream remains intact, and how vivid it is.

Age: Over time, a person is likely to experience changes in sleep timing, structure, and electroencephalographic (EEG) activity.

Evidence suggests that dream recall progressively decreases from the beginning of adulthood, but not in older age. Dream also become less intense. This evolution occurs faster in men than women, with gender differences in the content of dreams.

Gender: A study of dreams experienced by 108 males and 110 females found no differences between the amount of aggression, friendliness, sexuality, male characters, weapons, or clothes that feature in the content.

However, the dreams of females featured a higher number of family members, babies, children, and indoor settings than those of males.

Sleep disorders: Dream recall is heightened in patients with insomnia, and their dreams reflect the stress associated with their condition. The dreams of people with narcolepsy may a more bizarre and negative tone.

Dream recall and well-being

One study looked at whether dream recall and dream content would reflect the social relationships of the person who is dreaming.

College student volunteers were assessed on measures of attachment, dream recall, dream content, and other psychological measures.

Participants who were classified as “high” on an “insecure attachment” scale were significantly more likely to:

  • report a dream
  • dream frequently
  • experience intense images that contextualize strong emotions in their dreams

Older volunteers whose attachment style was classed as “preoccupied” were significantly more likely to:

Dream recall was lowest for the “avoidant” subjects and highest for the “preoccupied” subjects.


Basic Brain Supplements

I could (and would love to) start writing about getting your general health in order. But this is an article about lucid dreaming supplements. If you can't get all your nutrients through food, at least be nice to your brain and prepare it for quality sleep and dreaming with these basic supplements:

Multivitamins

This acts as a band aid for any nutritional deficiencies you may have. It will optimize functioning of your neurons and brain in general (remember the IQ study). The most popular multivitamin on Amazon is MegaFood One Daily.

Magnesium

Magnesium is used in many places ranging from the brain to your muscles. And yet 68% of people get too little of it in their regular diet 2 . It has been dubbed the "relaxation mineral" and is used by many to promote calm and optimal brain function.

Never get a magnesium oxide supplement. This is a cheap form and only 10% is actually absorbed by your body 3 . Besides, it'll just act as a laxative. Get the good stuff: Nature Made High Potency Magnesium.

Fish oil

Many people know that fish oil optimizes the brain. It's been used to improve concentration and capability to learn in essence it contains building blocks for your brain. Try the bestselling Signature Collection Omega-3 Fish Oil.

Lastly, the above supplements are intended for long term use. Take them daily. Only then consider additional lucid dream supplements.

Ask yourself: would you install a nitro upgrade in a car that has been poorly maintained? That's what you're doing when you use dream supplements before getting the basics right.


Affiliations

Department of Biology, Institute of Biology and Earth Sciences, Pomeranian University in Słupsk, Arciszewski Str., 22b, 76-200, Słupsk, Poland

Natalia Kurhaluk & Halyna Tkachenko

Department of Ecology and Nature Protection, National State University of Chernihiv, Chernihiv, Ukraine

Department of Human Physiology, Medical University of Gdańsk, Gdańsk, Poland

Pawel J. Winklewski & Magdalena Wszedybyl-Winklewska

Department of Clinical Anatomy and Physiology, Pomeranian University in Słupsk, Słupsk, Poland

You can also search for this author in PubMed Google Scholar

You can also search for this author in PubMed Google Scholar

You can also search for this author in PubMed Google Scholar

You can also search for this author in PubMed Google Scholar

You can also search for this author in PubMed Google Scholar

Corresponding author


Thread: Menthol as a Dream Enhancer

It has recently occurred to me that menthol might actually be a powerful dream enhancer and potential lucid aid, if used correctly. In order to test this out, I've decided to keep this research log. Since menthol is ridiculously easy to obtain for just about anyone, in the form of cough drops, essential oils, or possibly even pure crystals, you should feel free to post here if you give it a shot to contribute. But if not, that's fine too. I'll be giving a summary of why I think menthol can be so useful, followed by some past evidence and my first experience with it so far. Further experiences will be listed in successive posts.

03-18-2013 Update: Hey guys! I just wanted to add something here since this thread seems to be getting a lot of activity lately. Keep in mind that my theory here about how the way menthol works was just my first big one, but we've found out a lot more about it since I made this post and come up with lots of new (possibly coexistent) theories, and the picture just seems to be getting bigger so don't just take anything as fact yet! We've still got a lot to discover so just keep an open mind and consider the angles. If you want to see more of the theories you can either read through the thread or just come to the end and see what we're focusing on at th/e moment, it's generally the most up to date anyway. That's all for now!

Click on a list item to jump to that section.

Excuse me if I get a little technical here, but I'm going to try to give a good description of just exactly why I think menthol is effective at enhancing dreams. Most of this is actually documented, and some of it is hypothesizing based on those documents. Feel free to criticize, ask for references, or add comments to anything I have to say here.

I'll start with a description of each of these. Melanopsin is "a photopigment found in specialized photosensitive ganglion cells of the retina that are involved in the regulation of circadian rhythms, pupillary light reflex, and other non-visual responses to light." (Wikipedia) Essentially, melanopsin responds to light, and the more melanopsin you have the more light you perceive. Melatonin, which most people here are probably already familiar with, is a hormone that is one of the core chemicals produced by the pineal gland to regulate the light-dark cycle and the difference between REM and NREM sleep. Melatonin production is suppressed during the light and enhanced during the dark, and melatonin is correlated with NREM. It is also known that melatonin receptor agonists, like melatonin, inhibit the effects of 5-HT2A agonists, which enhance REM sleep. For this reason, I believe it's actually deactivating the pineal gland that promotes dreams and dream-like experiences, not activating it as many people seem to believe. (Not that I believe they're working towards the wrong sensations and the like through meditation, they're just calling it the wrong thing.) Melanopsin responds most strongly to blue light, and therefore, melatonin is suppressed most strongly from blue light. The D2 receptor is a G protein-coupled receptor in the brain, and other parts of the body, that responds to dopamine and other endogenous and exogenous ligands. D2 mutations have been associated with mental diseases such as schizophrenia, and many drugs which activate D2 can create dream-like experiences while awake, while the dream-like experiences of hallucinogens that work through separate mechanisms (e.g., psychedelics, which work through 5-HT2A receptors) can be reversed by drugs which block activity at D2. Effects commonly associated with D2 activation include rewarding feelings and increased power or energy, enhanced libido, and self-perpetuating anxiety (such as in panic attacks), all of which can be seen in lucid dreams (like lucid nightmares, for the last one). Furthermore, it is known that damage to the dopaminergic areas of the brain can result in a loss of dreaming. With all of this considered, I find it very likely that D2 is a very important mechanism involved in dreams.

Now, how does this all connect? Well, anyone who has researched spiritual/religious experiences or psychedelic drugs enough should be familiar with the "white light experience". If not, then essentially what it is is a perception of light so blindingly bright that it encompasses your entire being. It's often associated with OBEs, NDEs, and high doses of hallucinogens, and can even be experienced in dreams by chance or through meditation. I believe that this white light is part of a balance in the brain, and can be both a cause and effect of upsetting this balance. Aside from the sensory distortions of psychedelics that appear even at low doses, which are not considered true hallucinations, this white light seems to go hand in hand with dreams and dream-like experiences. On an average night your brain will block out this perception of white light as part of the dream process just like it blocks out your normal perception of entering sleep paralysis every night before you start dreaming, but it's still going on in the background. It's this white light that causes melatonin levels to drop to their lowest, inhibiting NREM and allowing REM dreams to form. As I mentioned before, the action of hallucinogens can traced through the D2 receptor, and all of these hallucinogens (especially direct D2 agonists, like salvia) can cause the white light experience. This is because melanopsin-containing ganglion cells express D2 receptors, and activating those receptors thereby increases melanopsin concentrations and inhibits melatonin production.

So there's the idea behind why the D2 receptor is important, which is significant in my explanation of menthol's usefulness. Clearly, activating this receptor is very useful as it directly enhances the mechanism by which dreams are formed. However, dopamine itself, while activating this receptor, also activates other dopamine receptors which promote wakefulness and energy, and overall will be harmful to keeping yourself in a dream. So, how do we go about activating D2 in a more efficient way?

Phenethylamine is another endogenous D2 agonist, a trace amine that exists naturally in the brain. Unlike dopamine, its action is much more selective in this respect, working directly on D2. Interestingly, D2 receptors actually act as a kind of flood control, lowering dopamine levels when activated. Since dopamine itself is already activating other receptors when it activates D2 receptors this effect is insignificant, however phenethylamine uses this method to directly block dopaminergic effects in certain areas of the brain, even directly blocking the effects of dopamine reuptake inhibitors like cocaine, while still creating the dream effects of D2. The CB1 receptor is another G protein-coupled receptor which responds to endocannabinoids, and drugs like THC (cannabis) and synthetic cannabinoids such as JWH-018 (Spice, K2). It is responsible for the psychoactive effects of these drugs.

It has been known for some time that THC increases endogenous levels of phenethylamine, but it would appear that the mechanism by which this occurs is still elusive. Very little is known about this phenethylamine boost other than the fact that it happens, and it doesn't seem to be a very well-researched subject matter. However, it does seem to be the case, at least. Many drug users in certain experimentalist groups have been testing the effects of pure phenethylamine and found it to produce the same type of psychedelic dissociation produced by cannabinoids, including the potential anxiety effects at high doses, all from D2 activation. The bad thing about this is that phenethylamine alone has effects on the peripheral nervous system which would not exactly be desired for a dream aid, whereas cannabinoids seem to release it only in areas of the brain involved in creating its dream-like effects, but of course, CB1 agonists have other effects as well involved in inhibiting short-term memory, clearly limiting their usefulness as dream aids.

From this point on an amount of guesswork is required, so please keep that in mind as you read. One of the core effects of CB1 agonists, which appears to lend itself to functional selectivity by different agonists, seems to be releasing dynorphins. Dynorphins are a class of endogenous opioid peptides that bind to certain receptors in the brain, which I'll go further into in a little bit. They are involved in a large number of processes which includes, most significantly for this discussion, circadian rhythms. They also directly lower the production of dopamine, block the effects of dopamine reuptake inhibitors, cause dysphoria and/or anxiety, and downregulate D2 receptors, while lowering dynorphin levels upregulates D2. This would imply that dynorphins are causing a direct activation of D2, as this relationship is how the brain creates tolerance. If you've read this far then you can probably already see where I'm going with this. Though there doesn't seem to have been any research done on the matter, I find it very likely from all these comparisons that dynorphins stimulate the release of phenethylamine, and that this is how CB1 agonists like THC create their dream-like effects. In fact, mice (or maybe rats, I'd have to pull up the article again) that were lacking in dynorphins were found not to have the anxiety reaction to THC, even though they should have still gotten it from phenethylamine if it was being released through a separate mechanism. So now the important question is, how are dynorphins achieving this?

The kappa-opioid receptor is the G protein-coupled receptor which binds dynorphins as its endogenous ligands. This makes dynorphins analogous to the mu-opioid receptor's endorphins. Drugs that bind to this receptor are known to cause hallucinations, though the recreationally used drugs that activate it (DXM, salvia) bind to other hallucinogenic receptors as well. Nonetheless, there are lesser known opioids, such as pentazocine, which have a strong kappa-opioid binding affinity in addition to their mu-opioid effects that are known to be self-limiting as analgesics because of their tendency to cause dysphoria/anxiety and hallucinations at high doses. Though dynorphins do have other minor binding affinities, it is very likely, if they really do increase concentrations of phenethylamines, that they do it through this receptor.

Now, the important part: menthol is a kappa-opioid agonist. It is a weak agonist, but an agonist all the same. For all of the enthusiasts out there, let me put a big DISCLAIMER here: I am not suggesting in any way, shape, or form that menthol is a viable candidate for recreational use as a hallucinogen. Menthol has other effects aside from its kappa-opioid agonism which may or may not create potentially dangerous side effects at doses that would be required for a full hallucinogenic effect. I am ONLY suggesting that it may be used as an effective dream enhancement aid because the doses required are much smaller and known to be safe. Any recreational abuse of menthol is done at your own risk. Believe me, it doesn't seem like I should have to say that, but I'm sure that I do, and it doesn't hurt to play it safe.

Anyway, the point by now should be clear. Kappa-opioid agonists seem to have fewer memory-limiting effects than cannabinoids, at least from what I've been able to find, and therefore are a better choice for dream enhancement. They surely seem to enhance dreams and recall in a more reliable way than cannabinoids, in any case. Due to the potential release of phenethylamine in only the safe parts of the brain like cannabinoids, they should also increase activity at D2 in the areas of the brain involved in dreaming, increasing melanopsin output and lowering melatonin production. And that is, in summary, why I think it works.

In this section I'm just going to reference a thread I responded to a few months ago, and add my experience with menthol thus far. This is what's made me consider menthol as an effective dream enhancer.

This thread was a major player in my decision to test menthol out, after I'd looked far enough into its mechanism of action: Does anyone have these really messed up dreams? And what causes them? The thread creator was having intense nightmares and was wondering why, and it turned out that they stopped after they stopped consuming a very large quantity of menthol cough drops every night. This would correlate with strong D2 activation (the dysphoria/anxiety), but could actually be overcome if lucid to make for an intensely vivid dream. though, nightmarish doses are certainly not a requirement. At the time I had suggested to the thread creator that the menthol cough drops may have been causing their nightmares, and it turned out to be correct but I didn't think too much into it at the time because I was focused on other things. Here are just a few excerpts from the thread which highlight its point.

So, for the past few days I've been having these crazy violent dreams but they aren't like normal nightmares I've had before, they're just these REALLY intense dreams, where I feel REALLY intense emotion and sensations, and they're like REALLY INTENSELY MESSED UP. And I remember every detail, like they feel totally real except for the strange. ness.

But now I'm sick and having them, so maybe I'm just staying a bit more aware or it's because I'm eating so many cough drops or I DUNNO?


What is the mechanism by which Melatonin increases dream vividness and intensity in humans? - Biology

Bi/CNS 163. Sleep and Dreams

As we have discussed in previous lectures, the brain is the organ in the body that is most affected and at the same time responsible for sleep and changes during sleep. It is therefore fundamental to understand what goes on inside the brain while we sleep. In particular, we would like to know which neuronal networks and chemical systems are activated during the different stages of sleep and what neuronal commands are responsible for sleep-wake transitions and sleep stage changes during the sleep period.

This is a very active area of sleep research that has its roots in the paradigm-shifting work of Bremer and Magoun and Moruzzi discussed previously. By making lesions in specific areas of the cat brainstem they managed to convincingly show that sleep is not a passive "shut-down" mechanism but that there are neuronal mechanisms that actively induce sleep.

cerveau isolé : transection through the brainstem between the superior and inferior colliculi. The cat survived for a few days ans showed permanent synchronized EEG and pupillary constriction (comatose state).

encéphale isolé : transection at the caudal end of the medula, just above the spinal cord. The cat showed normal sleep and waking cycles. The EEG showed periodic episodes of synchronized and desynchronized activity. It was able to track objects with the eyes.

"Midpontine cats". Transection just caudal to the cerveau isole preparation. The cat was awake 70-90 % of the time (as opposed to 30-40 % in normal cats). Cats show pupillary dilation, can track visual stimuli and show accomodation. When cortical synchrony is observed, visual stimuli have no effect.

Another reason to study the chemistry of sleep is that we may gain insights into the evolution of sleep. Evolution is natural selection acting over mutations. Enourmous changes in behavior or sleep patterns are ultimately dependent on spatial and temporal changes in the concentrations of different molecules, in particular of specific neurotransmitter systems as described in more detail below. Studying the evolution of sleep-relevant molecules can give important insights into how sleep evolved.

A general problem in neuroanatomy is that we are still talking at the level of hypothalamus, amygdala, hippocampus, visual cortex. This is equivalent to describing american people, russians and french. Saying that neurons in the hippocampus are active during sleep is similar to saying that american people like horror movies or fries. It is true for some but not necessarily true for everyone. There are approximately 10 11 neurons in the human brain (actually quite more than the population in the world). It is most certain that each neuron is not unique as each person is but still, talking at the level of nuclei is an enormous generalization. Much more work is still needed to understand which specific molecules, being released from which specific neurons and reaching which specific receptors in certain neurons are relevant for the changes during sleep. There are lots of fascinating questions to be addressed.

Several tools and approaches have been taken to study which brain nuclei and pharmacological circuits are activated during sleep:

  • Lesions
  • Chemical inactivation
  • Reversible cooling
  • Electrical stimulation
  • Neuronal recordings
  • Imaging the brain! (PET and fMRI)
  • TMS (trans-cranial magneting stimulation)

In each of these cases, the behavioral arousal of the subject can be studied as well as the EEG patterns of de-synchronization/synchronization of the brain.

One of the oldest theories about the induction of sleep states that a fatigue or toxin substance gets accumulated and induces the sleep state. Initially, it was thought that this substance should reside in the blood. However, the fact that Siamese twins with a common circulatory system sleep independently argues against a common sleep-inducing factor in the blood (Alekseyeva, 1958).

But maybe this putative sleep factor is not in the blood but in the brain. In order to test this idea, Legrende and Pieron (1913 ) kept dogs awake for several days. Then, they extracted cerebrospinal fluid from these animals and were able to induce sleep by injecting the fluid into the ventricular system of non-sleep deprived dogs.

It should be mentioned, however, that from subjective reports, sleepiness and tiredness have a circadian rhythmicity which cannot be explained by the simple accumulation of a sleep-inducing factor (Kleitman).

Melatonin has gained considerable attention recently as non-hazardous sleep-inducing pills. It is also widely used to combat the effects of jet-lag. It is a natural hormone produced by the pineal gland (top of the midbrain, between the superior colliculi). It only affects the latency to sleep and not the sleep structure. It seems to have a powerful hypnotic effect on birds but, interestingly, it seems to induce wakefulness when applied to rats during the daytime.

Several other substances have been suggested to have hypnogenic properties:

    • Muramyl peptides
    • Interleukin-1
    • Adenosine
    • Prostaglandin D-2
    • Cis 9,10 -octadecenoamide, a long fatty-acid amide

    Sleep is an active process

    No one has found neurons that "lack energy and need to sleep".

    No one has found neurons that run-out of neurotransmitters during the awake state and need to sleep to replenish them.

    There is no universal decline in firing rate during sleep. Neurons in some areas decrease their activity during sleep while neurons in other areas actually increase their firing. This is valid both for NREM as well as REM sleep. Furthermore, this has been observed both electrophysiologically and by functional imaging studies of the human brain (see below).

    It's not the absence of sensory stimulation that causes sleep. The body sensory stimulation can be severed and the animal still shows wake-sleep cycles.

    Arousal and sleep mechanisms

    As discussed previously, making lesions in the brainstem reticular formation in cats produced slow-wave activity in the EEG and inactivity as in the coma state in humans. Some of the usual concerns about lesion experiments include the fact that the experiment may be unwillingly and without knowing damaging fibers of passage. That if a lesion in area X produces a given deficit or state, it is possible that there are actually axons going from area Y to area Z that go through area X and are being concomitantly damaged and responsible for the deficits. On the other hand, if there is no deficit, it could be argued that area X is indeed important but that recovery and plasticity are helping the brain cope with the damage.

    An elegant and landmark experiment was carried out by Moruzzi and Magoun (1949) to further establish the importance of activity in the brainstem in regulating sleep/wake cycles. They showed that electrical stimulation of the brainstem reticular formation yields a state of arousal in cats.

    Furthermore, single unit recording studies show that there is a correlation between the firing rate of neurons in the brainstem reticular formation and arousal. These neurons project to non-specific thalamic neurons that show similar properties and direct their output all over the cortex.

    The hypothalamus is an interesting structure. It is involved in regulating heart rate, blood pressure, thirst, hunger, sex, wakefulness and sleep!

    The hypothalamus is important in regulating the circadian rhythm. Damage to the hypothalamus in rats disrupts otherwise organized daily rhythms. A particular area of the hypothalamus, called the suprachiasmatic nucleus (because it is above the optic chiasm which is where the information from the two eyes cross) seems to be particularly important for the circadian regulation. This nucleus receives direct input from the retina, thus providing a mechanism to entrain the circadian rhythm dependent on the light in the environment.

    If an area of the hypothalamus, called the basal forebrain is damaged, animals become hypervigilant. Furthermore, electrical stimulation of this region can induce slow wave sleep.

    Dopamine is a neurotransmitter released by the substantia nigra. Lesions in this region cause a comatose state in cats but not in rats (the reason for this difference is unclear). Patients with Parkinson's disease show damage in the substantia nigra neurons. They also display signs of progressive immobility. Antidopaminergic drugs (used to combat schizophrenia) also induce hypoactivity and lack of facial expressivity. The dopaminergic system seems to be more involved in the initiation of movement than on conciousness or the lack thereof. There are also dopamine releasing neurons in the posterior hypothalamus. Lesions in the substantia nigra produces unresponsiveness and immobility.

    Several lines of evidence suggest an important role for noradrenalline and monoamines in general in being responsible for the arousal state.

    Noradrenaline (NA) is released (among others) by the locus coeruleus in the pons. Amphetamine facilitates the release of dopamine and NA and retards re-uptake. The effects of amphetamine dissapear after lesions in the pontine-midbrain reticular formation. Cocaine inhibits reuptake of catecholamines. There is also prolonged and intense arousal by MAO inhibitors (mono-amine oxidase inhibitors). Conversely, arousal is decreased by inhibition of catecholamine synthesis.

    The electrodes in the stimulation experiment of Moruzzi and Magoun were very close to this noradrenergic system.

    Reserpine, which produces a state of inactivityy and tranquilization acts by depletion of monoamines. The effect is reversed by administration of L-dopa.

    Clinical studies have also provided evidence for the involvement of dopamine and norepinephrine neurons in conditions of akinesia and coma.

    Raphe nuclei (Greek seam, suture)

    Disconnecting it from the rest of the cerebrum causes almost constant arousal. Lesions cause 3-4 day insomnia (in cats) NREM sleep slowly recovers (why this is so or what exactly happens during this recovery is unclear). Anesthetic injections have anti-sleep effects. Electrical stimulation (within the caudal solitary tract) induces sleep.

    Functional imaging provides a fascinating non-invasive tool to look at the changes in blood levels in the human brain while subjects are sleeping. For an introductory article on the physical and biological basis of functional imaging, see Raichle (1994). For an overview of studies of functional imaging during sleep, see Hobson (1998)

    There seems to be an overall decline in oxygen consumption during NREM sleep.

    The anterior cingulate cortex, the thalamus and the pontine brainstem are activated during REM.

    A fascinating question that people have studied for decades is whether the brain activation during REM is similar to that during the wake state. Using EEG measurements it is not easy to distinguish the awake state and REM sleep. The EOG (electro-oculogram) is thus required. Differences can also be found at the single-neuron or pharmacological level but many researchers had suggested that REM is the same as the waking state except for closed input-output. The imaging studies provide the first clear evidence to the contrary.

    Limbic and paralimbic regions of the brain are suggested to be involved in processing emotions as evidenced by neurophysiological, lesion and molecular studies in animals and humans. These areas are more activated during REM than during the awake state. This fits with our subjective recall of most dreams as being rich in emotional content. In particular, the amygdala is strongly activated during REM sleep.

    There seems to be a de-activation of pre-frontal cortex during REM sleep. It was suggested that dream-amnesia could be due to prefrontal deactivation.

    Visual areas are activated during REM sleep. This broadly correlates with the visuospatial vividness of dreams.

    It was suggested that the fictive movement depends on the activation of the basal ganglia or cerebellar nuclei.

    Scientists and philosophers have always discussed about the problem of consciousness. Recently, the neuroscience community has become particularly interested in this fascinating problem. Specific hypothesis and experiments have been suggested in order to address rigorously what the neuronal correlates of visual consciousness are. Crick and Koch have claimed that there must be a specific group of neurons that explicitly represent the contents of our moment-to-moment aware perception.

    In this regard, studies of sleep and dreams in particular may provide particularly relevant data. From a subjective point of view, it seems evident that we are perfectly conscious during our dreams. In particular, since most dreams have strong visual content (in non-congenitally blind people) we are visually aware during our dreams. We could therefore include one more constraint for the neurons that correlate with our visual perception. The neurons that represent our visual awareness should be activated when we see something, when we close our eyes and imagine it or when we are asleep and dream about the same thing.

    Crick and Koch have argued based on neurological and electrophysiological evidence that the activity in area V1 does not correlate with our visual awareness. It is therefore interesting to note that V1 does not seem to be activated during dreams. It is also quite fascinating to note that higher visual areas, particularly the temporal lobe is activated during sleep.

    Unresolved issues: hot topics for a Ph.D

    As fMRI gets better and better in spatial and temporal resolution it will be more and more fascinating to look more carefully at what happens in different brain areas during sleep.

    Sleep stages and brain activity (requires simultaneously recording EEG and fMRI work in progress).

    Correlation between dreams and brain activity (fMRI and wake-up subjects complications with this experiment).

    Molecular biology of sleep. Gene knock-outs and sleep patterns.

    A full list of references appears in the bibliography page

    Braun, A. R. and P. Herscovitch (1998). "Dissociated pattern of activity in visual corties and their projections during human rapid eye movement sleep." Science 279 : 91-95.

    Hofle, N., T. Paus, et al. (1997). "Regional cerebral blood flow changes as a function of delta and spindle activity during slow wave sleep in humans." Journal of Neuroscience 17 (12): 4800-4808.

    Lavie, P. (1996). The enchanted world of sleep . New Haven, Yale University Press.

    Macquet, P. and G. Franck (1996). "Functional neuroanatomy of human rapid eye movement sleep and dreaming." Nature 383 : 163-166.

    McCormick, D. A. and T. Bal (1997). "Sleep and arousal: thalamocortical mechanisms." Annual review of neuroscience 20 : 185-215.

    Mechoulam, R., E. Fride, et al. (1997). "Anandamide may mediate sleep induction." Nature 389 : 25-27.

    PorkkaHeiskanen, T., R. E. Strecker, et al. (1997). "Adenosine : a mediator of the sleep-inducing effects of prolonged wakefulness." Science 276 : 1265-1268.

    Steriade, M., D. A. McCormick, et al. (1993). "Thalamocortical oscillations in the sleeping and aroused brain." Science 262 : 679-685.

    Hobson, J. A., E. F. Pace-Schott, et al. (1998). "To dream or not to dream ? Relevant data from new neuroimaging and electrophysiological studies." Current Opinion in Neurobiology . 8 : 239-244.

    Raichle, M. (1994). "Visualizing the mind." Scientific American April : 58-64.

    Crick, F. (1994). The astonishing hypothesis . New York, Simon & Schuster.

    Crick, F. and C. Koch (1998). "Consciousness and Neuroscience." Cerebral Cortex 8 : 97-107.


    Watch the video: What is the mechanism by which the AIDS virus causes deficiency of immune (October 2022).