How Brain Health & Neurotransmitters Affect Sleep

What Happens During Sleep? | UPMC Sleep Medicine Resources

How Brain Health & Neurotransmitters Affect Sleep

Many people think of sleep as a passive activity, but our brains are actually very active during sleep. Moreover, sleep affects our daily functioning and our physical and mental health in many ways.

Nerve-signaling chemicals called neurotransmitters control whether we are asleep or awake by acting on different groups of nerve cells, or neurons, in the brain. Neurons in the brainstem, which connects the brain with the spinal cord, produce neurotransmitters such as serotonin and norepinephrine that keep some parts of the brain active while we are awake.

Other neurons at the base of the brain begin signaling when we fall asleep. These neurons appear to “switch off” the signals that keep us awake. Research also suggests that a chemical called adenosine builds up in our blood while we are awake and causes drowsiness. This chemical gradually breaks down while we sleep.

Five phases of sleep

During sleep, we usually pass through five phases of sleep: stages 1, 2, 3, 4, and REM (rapid eye movement) sleep.

These stages progress in a cycle from stage 1 to REM sleep, then the cycle starts over again with stage 1.

We spend almost 50 percent of our total sleep time in stage 2 sleep, about 20 percent in REM sleep, and the remaining 30 percent in the other stages. Infants, by contrast, spend about half of their sleep time in REM sleep.

  • Stage 1 During stage 1, which is light sleep, we drift in and sleep and can be awakened easily. Our eyes move very slowly and muscle activity slows. People awakened from stage 1 sleep often remember fragmented visual images. Many also experience sudden muscle contractions called hypnic myoclonia, often preceded by a sensation of starting to fall. These sudden movements are similar to the “jump” we make when startled.
  • Stage 2 When we enter stage 2 sleep, our eye movements stop and our brain waves (fluctuations of electrical activity that can be measured by electrodes) become slower, with occasional bursts of rapid waves called sleep spindles.
  • Stage 3 In stage 3, extremely slow brain waves called delta waves begin to appear, interspersed with smaller, faster waves.
  • Stage 4 By stage 4, the brain produces delta waves almost exclusively. It is very 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 during deep sleep do not adjust immediately and often feel groggy and disoriented for several minutes after they wake up. Some children experience bedwetting, night terrors, or sleepwalking during deep sleep.
  • REM sleep When we switch into REM sleep, our breathing becomes more rapid, irregular, and shallow, our eyes jerk rapidly in various directions, and our limb muscles become temporarily paralyzed. Our heart rate increases, our blood pressure rises, and males develop penile erections. When people awaken during REM sleep, they often describe bizarre and illogical tales – dreams.

The first REM sleep period usually occurs about 70 to 90 minutes after we fall asleep. A complete sleep cycle takes 90 to 110 minutes on average. The first sleep cycles each night contain relatively short REM periods and long periods of deep sleep.

As the night progresses, REM sleep periods increase in length while deep sleep decreases. By morning, people spend nearly all their sleep time in stages 1, 2, and REM.

People awakened after sleeping more than a few minutes are usually unable to recall the last few minutes before they fell asleep.

This sleep-related form of amnesia is the reason people often forget telephone calls or conversations they've had in the middle of the night.

It also explains why we often do not remember our alarms ringing in the morning if we go right back to sleep after turning them off.

Dreaming and REM sleep

We typically spend more than 2 hours each night dreaming. Scientists do not know much about how or why we dream. Sigmund Freud, who greatly influenced the field of psychology, believed dreaming was a “safety valve” for unconscious desires. The strange, illogical experiences we call dreams almost always occur during REM sleep.

REM sleep begins with signals from an area at the base of the brain called the pons These signals travel to a brain region called the thalamus , which relays them to the cerebral cortex – the outer layer of the brain that is responsible for learning, thinking, and organizing information.

The pons also sends signals that shut off neurons in the spinal cord, causing temporary paralysis of the limb muscles. If something interferes with this paralysis, people will begin to physically “act out” their dreams – a rare, dangerous problem called REM sleep behavior disorder.

A person dreaming about a ball game, for example, may run headlong into furniture or blindly strike someone sleeping nearby while trying to catch a ball in the dream.

REM sleep stimulates the brain regions used in learning. deep sleep, REM sleep is associated with increased production of proteins. One study found that REM sleep affects learning of certain mental skills. People taught a skill and then deprived of non-REM sleep could recall what they had learned after sleeping, while people deprived of REM sleep could not.

Sleep influenced by food, medications, chemicals, temperature

Since sleep and wakefulness are influenced by different neurotransmitter signals in the brain, foods and medicines that change the balance of these signals affect whether we feel alert or drowsy and how well we sleep.

  • Caffeinated drinks such as coffee and drugs such as diet pills and decongestants stimulate some parts of the brain and can cause insomnia, or an inability to sleep.
  • Many antidepressants suppress REM sleep.
  • Heavy smokers often sleep very lightly and have reduced amounts of REM sleep. They also tend to wake up after 3 or 4 hours of sleep due to nicotine withdrawal.

Many people who suffer from insomnia try to solve the problem with alcohol – the so-called night cap. While alcohol does help people fall into light sleep, it also robs them of REM and the deeper, more restorative stages of sleep. Instead, it keeps them in the lighter stages of sleep, from which they can be awakened easily.

People lose some of the ability to regulate their body temperature during REM, so abnormally hot or cold temperatures in the environment can disrupt this stage of sleep.

If our REM sleep is disrupted one night, our bodies don't follow the normal sleep cycle progression the next time we doze off. Instead, we often slip directly into REM sleep and go through extended periods of REM until we “catch up” on this stage of sleep.

People who are under anesthesia or in a coma are often said to be asleep. However, people in these conditions cannot be awakened and do not produce the complex, active brain wave patterns seen in normal sleep. Instead, their brain waves are very slow and weak, sometimes all but undetectable.

Source: https://www.upmc.com/services/pulmonology/our-services/sleep-medicine/resources/during-sleep

These Neurotransmitters Are Probably Keeping You Up At Night

How Brain Health & Neurotransmitters Affect Sleep
This article is more than 2 years old.

(Photo by China Photos/Getty Images)

What happens neurologically that causes us to wake up from sleep? originally appeared on Quora: the knowledge sharing network where compelling questions are answered by people with unique insights.

Answer by Colin Gerber, Neuroscientist, on Quora:

There are at least eleven (almost definitely more) neurotransmitters and hormones that play intimate roles in the sleep-wake cycle. I will go through a list of all of them and talk a little bit about what they do.

There has been so much research done on this area and so many mechanisms and interactions have been found that it would be almost impossible to pull everything together in this answer.

I will try to give a quick summary and some links to papers in relation to each neurotransmitter and hormone.

  • GABA: GABA is one of the more prevalent neurotransmitters in the brain and is usually responsible inhibition. GABA release is often seen as a way to shut down or down regulate neurons. One of the main areas GABA is involved in for the sleep-wake cycle is the posterior hypothalamus (PH). The stimulation of the neurons in the PH are known to contribute to wakefulness. It has been seen that increased levels of GABA in this area contribute to inducing sleep [1]. (Source)
  • Orexin (hypocretin): Orexin is a neurotransmitter that is linked to arousal and wakefulness and is almost exclusively produced in the hypothalamus. It has been shown that the most common type of narcolepsy is caused by a loss of orexin through the destruction of orexin producing cells. It is thought that orexin is responsible for regulating many different systems involved with sleep and stabilizing both awake and sleep states. Some of the systems orexin regulates are dopamine, norepinephrine, histamine, and acetylcholine systems. It is also thought that the orexin system is responsible for integrating different influences such as metabolic, circadian and sleep debt to decide what state the body should be in (asleep or awake) [2,3,4].
  • Glutamate: Glutimate is the most common neurotransmitter in the brain and the main excitatory neurotransmitter. Interestingly it is also the precursor for GABA (which I talked about above) which is the main inhibitory neurotransmitter in the brain [5]. Glutamate is involved in a variety of areas of the sleep-wake cycle. Glutamatergic input to the oral part of the pontine reticular formation (PnO) is thought to regulate sleep duration [6]. It has also been seen that glutamatergic inputs in the posterior hypothalamic region (PH-TMN) help regulate both REM sleep and wakefulness [7].
  • Acetylcholine: Acetylcholine (ACh) is a neurotransmitter that is often associated with the activation of muscles but is also involved in the cholinergic system which often results in inhibitory actions [8]. The most important ACh neurons that are involved with the sleep-wake cycle are located in the pons and basal forebrain. It has been seen that the ACh neurons in these areas are very important for the initiation of REM sleep. It has also been observed that ACh levels are at their highest during REM sleep and waking states [9]. (Source)
  • Norepinephrine: Norepinephrine can act as both a neurotransmitter and a hormone. It is probably best known as a stress hormone and one of the main components in the flight-or-fight response [10]. Norepinephrines activity in the locus coruleus (LC) is the most important with regards to the sleep-wake cycle.  This is one of the main areas involved in arousal from sleep. Increased norepinephrine also decreases REM sleep [9,11]. (Source)
  • Dopamine: Dopamine is a neurotransmitter that is best known for it's role in the regulation of motor function as well as it's depletion during Parkinson's Disease which leads to motor dysfunction. Dopamine (basal ganglia) seems to regulate sleep-wake states and helps control when we enter each. Dopamine can down regulate melatonin, which is partly responsible for causing sleepiness, which can greatly contribute towards waking up from sleep [12, 13].
  • Melatonin: Melatonin is the hormone that is most commonly associated with the sleep-wake cycle. Levels of melatonin vary throughout the day (and night) which helps regulate circadian rhythms in the body [14]. Melatonin levels are high at night (during sleep) and low during the day (during wakefulness). The levels of melatonin are regulated by the suprachiasmatic nucleus of the hypothalamus which reacts to the amount of light in the environment. So the darker it is outside of the body, the more melatonin there is [15].
  • Serotonin: Serotonin is a neurotransmitter that is commonly associated with depression (or the lack of serotonin is associated with it). Serotonin is produced almost solely in the Raphe nuclei [16]. Serotonin has similar effects on the sleep-wake cycle to those of norepinephrine. Serotonin helps to maintain arousal and cortical responsiveness as well as inhibiting REM sleep [9,17]. (Source)
  • Cortisol: Cortisol is a steroid hormone and is often released in response to stress [18]. It has also been implicated that a disruption of regular cortisol production can cause insomnia [19]. Cortisol is released by the adrenal gland and helps the body maintain homeostasis.
  • Growth hormone-releasing hormone (GHRH): GHRH's main activity is causing the anterior pituitary gland to release growth hormone. It also promotes slow-wave sleep [20]. When production of GHRH is increased slow-wave sleep is enhanced [21].
  • Corticotropin-releasing hormone (CRH): Corticotropin-releasing hormone is a peptide hormone involved in stress response. It has been shown that injections of CRH promote wakefulness and inhibit slow-wave and REM sleep [22,23].
  • Adenosine: Adenosine is an inhibitory neurotransmitter that is involved in promoting sleep. After you wake up, adenosine levels begin to build up in your brain throughout the day causing you to become more and more sleepy. People throughout history have tried to fight this by taking adenosine antagonists (which block the sites where adenosine normally binds in the brain.) The most common of the adenosine antagonists is caffeine [24,25].

Summary: So as you can see, waking up is a very complex system that involves many different areas of the brain and many different neurotransmitters and hormones.

If you were to choose which are most important I would say that norepinephrine is important for arousal along with having low levels of melatonin and adenosine (opposed to high).

Glutamate is important for regulating the length of sleep and orexin regulates the levels of many neurotransmitters involved in waking including norepinephrine.

[1] GABA release in posterior hypothalamus across s… [Am J Physiol. 1996]

[2] Orexin

[3] Orexins, energy balance, temperature, sleep-wake cycle

[4] http://www.semel.ucla.edu/sites/…

[5] Glutamate receptor

[6] Sleep duration varies as a function of glutamate… [J Neurochem. 2011]

[7] Rapid changes in glutamate levels in the posterior hypothalamus across sleep-wake states in freely behaving rats

[8] Acetylcholine

[9] http://web.mst.edu/~rhall/neuros…

[10] Norepinephrine

[11] http://academicdepartments.musc….

[12] Feel-Good Brain Chemical's Role in Sleep

[13] Dopaminergic control of sleep-wake states.

[14] Melatonin

[15] http://www.ncbi.nlm.nih.gov/pmc/…

[16] Serotonin

[17] http://www.ncbi.nlm.nih.gov/pubm…

[18] Cortisol

[19] http://naturalmedicinejournal.ne…

[20] Growth-hormone-releasing hormone

[21] Growth hormone-releasing hormone and interleukin-1 i… [FASEB J. 1993]

[22] Corticotropin-releasing hormone

[23] Central Deficiency of Corticotropin-Releasing Hormone Receptor Type 1 (CRH-R1) Abolishes Effects of CRH on NREM But Not on REM Sleep in Mice

[24] Adenosine

[25] THE BRAIN FROM TOP TO BOTTOM

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Source: https://www.forbes.com/sites/quora/2016/10/05/these-neurotransmitters-are-probably-keeping-you-up-at-night/

Sleep Deprived? Mind your dopamine

How Brain Health & Neurotransmitters Affect Sleep

Most of us will suffer sleep deprivation at one time or another. I'm not talking our usual state of broken sleep, 5 hours a night, or something else. I'm talking a full night without sleep, the kind many people experience in the army, with a brand new (or not so brand new) baby, or more frivolously (I hope), in college.

We all know what sleep deprivation does to us. We're unable to pay attention. We're often cold or hot. We can't think straight, we start doing very strange things (you would not BELIEVE the crazy dances I've made up…), and of course, we're really, really tired.

But why do these symptoms happening? What's going on in the brain during sleep deprivation to explain this behavior? Well, in part, it might be changes in your D2 receptors.

(Source)

Volkow et al. “Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatumin the Human Brain” Journal of Neuroscience, 2012.

There are lots of signs that point toward the involvement of the neurotransmitter dopamine in wakefulness. Drugs that increase levels of dopamine in brain (including, but not limited to, drugs cocaine, amphetamine, meth, and Ritalin) also increase feelings of wakefulness.

Increasing dopamine in the brain via genetic alterations, getting rid of the dopamine transporter in a mouse, stopping dopamine from getting recycled, produces a mouse that sleeps less.

Diseases that are characterized by low dopamine levels, Parkinsons, also have daytime sleepiness.

But a neurotransmitter is only as good as its receptor. Dopamine has two main types of receptors, and the current hypothesis is that the wakefulness promoting effects of dopamine may be controlled partially by the D2 type receptor. Antipsychotics, which block D2 type receptors, make people sleepy, and previous studies showed decreased D2 binding in the brains of sleep deprived people.

But the question is: what is causing the decreases in D2 when people are sleep deprived? The authors of this study hypothesized that this was due to increased dopamine release, which would cause decreases in D2 receptors (this is a basic idea in pharmacology, when a group of receptors is overstimulated, some receptors will leave the membrane, making the membrane less sensitive to stimulation).

To test this hypothesis, they took a bunch of human volunteers, and either sleep deprived them overnight (they kept them in a facility with a nurse bugging them to keep their eyes open if they got drowsy), or kept them in the facility to get a good night's rest (all participants underwent both conditions).

In the morning, they looked at the D2 receptors in the striatum of the brain, an area with loads of dopamine and associated with things arousal and reward.

To do this, they used positron emission tomography (PET), which uses a radioactive tracer (C-raclopride), which binds to D2 type receptors, allowing you to see how many are present.

They showed that D2 type receptor binding was definitely lower in sleep deprived people.

But what does this mean? Does it mean that there's more dopamine release when you're tired, decreasing the D2 type receptors? Or do the D2 type receptors decrease for some other reason? To look at this, the authors of the study treated the participants with methylphenidate (Ritalin), which increased the amounts of dopamine. They hypothesized that if sleep deprivation produced more dopamine release, the methylphenidate should produce larger increases in dopamine than in well rested patients.

Above you can see nice pretty pictures showing places where the methylphenidate produced larger or smaller changes in sleep deprived patients vs not…but overall there was no difference.

This means that the decrease in D2 type receptors that the authors see with sleep deprivation is NOT due to increases in DA release during sleep deprivation. They confirmed this with studies in rats, and showed that the sleep deprived rats showed no increases in dopamine, but showed similar D2 type receptor changes.

So what is going on? Unfortunately, the authors didn't go after that question, though they talk about a “different physiological mechanism”. They do hypothesize that adenosine might have something to do with it.

Adenosine is a neurochemical which you know best from your morning cup of coffee. Caffeine increases wakefulness by antagonizing adenosine receptors, and adenosine itself promotes sleepiness.

Not only that, one of the areas involved in this effect appears to be the striatum, the dopamine-rich area the authors were looking at in this study. Caffeine can increase D2 type receptor levels in this area.

So it seems the next thing to look at would be how adenosine and dopamine might be interacting following sleep deprivation (though unfortunately, they didn't look at it here).

So what does this mean? Well, the changes in D2 type receptors could help explain some of the other changes in behavior that come with sleep deprivation, changes increases in risk taking behavior, impulsivity, and drug relapse.

These are all things which increase when people are sleep deprived. So the changes seen in D2 type receptors could help explain show these behavioral changes occur.

But while we see changes in receptors, we still don't know why, and the proposed mechanism still needs to be tested.

Volkow, N., Tomasi, D., Wang, G., Telang, F., Fowler, J., Logan, J., Benveniste, H., Kim, R., Thanos, P., & Ferre, S. (2012). Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain Journal of Neuroscience, 32 (19), 6711-6717 DOI: 10.1523/JNEUROSCI.0045-12.2012

Source: https://blogs.scientificamerican.com/scicurious-brain/sleep-deprived-mind-your-dopamine/

Explanation of Neurotransmitters | Tuck Sleep

How Brain Health & Neurotransmitters Affect Sleep

Medications for insomnia and hypersomnia usually act on neural systems and affect, in some manner, neurotransmitters. Sleep aids tend to work on the GABA receptors in the brain, or melatonin receptors. Stimulants usually work on dopamine or acetylcholine systems.

This website covers all aspects of sleep; neurotransmitters are involved in sleep, waking, and the transitions between them. Brain chemistry is very complicated and scientists don’t totally understand how all the pieces fit together. Here we give a short description of major neurotransmitters.

Neurons (commonly called nerves) are a specific type of cell found in the body and the brain that carries electrical information. Their job is to receive a signal from a cell, convert it to an electric signal called an action potential and transmit this electric signal to another cell that could also be another neuron.

When they need to communicate to another cell or neuron, the first neuron sends a chemical called a neurotransmitter across the space between the two, over to the next cell.

Once at the second cell, the neurotransmitter binds to a receptor, telling the second cell what to do or telling another neuron if to send a signal and whether it should be a strong or a weak signal.

Among other things, neurotransmitters are responsible for spinal reflexes and sleep regulation. There are currently conflicting classifications of which chemicals in the brain are considered to be neurotransmitters. Following are neurotransmitters of interest to sleep researchers and that scientists agree are actually neurotransmitters.

GABA (gamma aminobuytric acid) is an amino acid derivative that acts as an inhibitory neurotransmitter, preventing or reducing certain nerve signals.

It controls nervous signals in the retina and the central nervous system, so insufficient GABA usually causes anxiety and even epileptic seizures. Drugs can temporarily increase GABA levels and in turn reduce anxiety, and offer anti-convulsive effects.

Some medicinal and recreational drugs reduce the natural level of GABA; these include alcohol, barbiturates and cannabinoids. The drugs that reduce GABA combined with serotonin depletion can cause depression which keeps addicts in the cycle of addiction.

Patients with spastic cerebral palsy have damaged nerves in the central nervous system that cannot properly absorb GABA, affecting motor or muscular skills.

GABA is not found in any significant amounts outside the brain. Indeed, GABA is pretty much unique to the central nervous system of mammals. Many sedatives and hypnotics are GABA agonists.

Glutamic acid, also known as glutamate, is an amino acid and is the most common neurotransmitter in the body. 80% of the brain’s neurons release glutamate.

Glutamate’s most vital function as a neurotransmitter is in cognitive activities memory and learning.

Scientists have pointed the finger at glutamic acid as being involved in epileptic seizures, probably since glutamate can also be a precursor for the synthesis of GABA.

Glutamate is involved arousal and anesthetic drugs seem to work at least partly by reducing neurotransmission normally regulated by glutamate. Lower-than-normal levels of oxygen in the blood – such as apnea causes – stimulates production of glutamate.

Acetylcholine was the first neurotransmitter to be discovered by scientists and its major function is in the voluntary movement of muscles, although it also has many other functions. It is involved in the scheduling of REM sleep.

The onset of Alzheimer’s disease happens when some regions of the brain have depleted acetylcholine. Neurons that interact with acetylcholine are found in plenty in the pons (above the medulla) and in the basal forebrain.

The preoptic area and anterior hypothalamus (together sometimes called POAH) are important in both REM and in regulation of the body’s temperature during sleep.

It is also to make the causal direction go the other way – by manipulating the POAH it is possible to include insomnia or sleepiness, and if the POAH is artificially warmed, the brain is induced to go into deep sleep.

The temperature of both the brain and the body fall during NREM sleep.  The longer the NREM-sleep episode, the more the temperature falls. By contrast, brain temperature increases during REM sleep.

Norepinephrine is the neurotransmitter most involved in the “fight or flight” response and other stressful situations, since it increases heart rate and blood pressure.

A catecholamine, It is intertwined with arousal, wakefulness, attentiveness, sleep and it is also involved in the formation of memories. Studies have shown that elevated norepinephrine levels are implicated in symptoms in some mood disorders.

Neurons in the locus coeruleus in the bottom of the brain stem respond to norepinephrine. When these neurons are stimulated, the cortical area of the brain becomes more active. Norepinephrine is therefore thought to be instrumental in causing people to wake up.

Indeed, the level of this neurotransmitter in the brain seems to rise in response to new stimuli. The concept of vigilance is tied up with norepinephrine although scientists don’t understand how.

Now when a person is in REM sleep, the cortex is aroused, but the levels of norepinephrine do not rise, in contrast to what happens during waking. Actually, the levels are at their lowest during REM and drugs that mimic norepinephrine affect sleep architecture by shortening the REM sleep period. Norepinephrine antagonists make the period longer.

Dopamine is another inhibitory neurotransmitter involved in voluntary movement and motivation. Sometimes called the “salience chemical” dopamine plays important roles in pleasure and subjective feelings of happiness. Alcohol, nicotine and some recreational drugs increase the level of dopamine.

Schizophrenia is linked to elevated levels of dopamine in the frontal lobes of the brain. Conversely, low levels of dopamine in the motor areas of the brain are implicated in Parkinson’s disease, causing muscle rigidity and uncontrollable muscle tremors.

Animal models of Parkinson’s disease and schizophrenia have found that dopamine plays an important role in regulating sleep.

Mice altered to have high dopamine levels in their brains are more sensitive than normal to caffeine and modafinil and have a stronger recovery reaction to sleep deprivation: following prolonged wakefulness they have move slow-wave sleep and total sleep than other mice.

Serotonin is involved in several important body functions such as memory, emotions, moods, appetite and thermoregulation, so it comes as no surprise the neurotransmitter is important in regulating sleep and waking also.

It makes people feel contented and safe. Serotonin deficiencies have been linked to depression, anger, OCD, sleep disturbances, irritable bowel syndrome and many other emotional and physical disturbances.

Serotonin is involved in arousal and keeping the higher brain functions operating during waking.

Does serotonin make one more sleepy or more awake?  Seemingly both. But given we need to sleep sometimes and to be awake at times, maybe more serotonin is generally a good thing.

 Scientists have found that serotonin directly promotes wakefulness and also promotes the formation of sleep-promoting brain factors, perhaps as part of an evolutionary negative feedback look.

 Orexinergic wake-promoting neurons also stimulate serotonergic neurons.

Experiments on animals that artificially increase levels of 5-Hydroxytryptophan (a biochemical precursor for both serotonin and melatonin) increase wakefulness immediately, followed by an increase in non-REM sleep.

 Serotonergic neurons inhibit sleep-promoting neurons and when serotonin levels increase, REM time decreases. In normal brain function, the release of serotonin is highest during wakefulness and has been found to decrease during NREM sleep.

It slows significantly during REM sleep, which is interesting given the possible connection between REM sleep and depression. (Antidepressant drugs seem to suppress REM.)

Steroids also participate in sleep regulation. Cortisol increases propensity to REM sleep and estrogen supplements appear to help post-menopausal women sleep, although this may be due to an indirect mechanism. Growth hormone-releasing hormone (GHRH) and corticotropin-releasing hormone also play parts in sleep regulation.

Orexin (Hypocretin) refers to several brain chemicals. They are excitatory neuropeptides that promote waking and suppress sleep.

The perifornical hypothalamic area of the brain is rich in neurons that have orexin receptors.

Animal tests involving orexin injections into the pontine reticular formation produced an increase in wakefulness and an increase in GABA levels. Narcoleptics have fewer orexin neurons. More on orexins.

Adenosine is produced by the body as a normal product of metabolism. We produce more when awake and active than when sleeping.

Adenosine plays a part in the sleep homeostatic process as it inhibits wake-promoting neurons.

These neurons are in the basal forebrain, and damage or changes to these neurons seems to play a part in the development of Alzheimer’s Disease. Caffeine seems to work by affecting adenosine.

Melanin is a common pigment in the body (it’s what makes tanned skin darker, among other things).  It is not the same as melatonin, although both are amino-acid derivatives, and melatonin was discovered by a dermatologist investigating skin pigmentation. Melanin-concentrating hormone is a cyclic neuropeptide that influences the distribution of melanin in the body.

melatonin, melanin-concentrating hormone (MCH) is also produced by the pituitary and is part of the weight (and maybe sleep) homeostatic processes.

 Scientists have identified two receptors in the body that are activated by the hormone, and there has been interest in developing antagonists to treat obesity and mental health problems. (Too much MCH is correlated with obesity.

) Detailed investigation has found MCH increases water intake and sugar intake

Recent research has suggested MCH plays a part in the complex sleep regulation system. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080035/) The receptor cells are spread throughout the central nervous system.  More research is required to figure this all out, but given the close association between appetite and sleep regulation, it would not be surprising if MCH plays a part in sleep.

Arousal and Sedation

Acetylcholine, dopamine, glutamate, histamine, norepinephrine, orexin, and serotonin are all active in promoting wakefulness.

Some neurons (brain cells) specialize in releasing certain neurotransmitters and scientists have found the firing rates of those neurons can vary with wakefulness and sleep.

Glutamate and histamine neuron firing rates are high during wakefulness and low during sleep

Orexin neurons have high firing rates during waking, especially during movement. They release orexins during quiet waking and are the lowest during sleep. Cholinergic cells (neurons that release acetylcholine) are more active during waking.

Dopamine release does not seem to vary with waking or sleeping. and serotonin, which is important in promoting both wakefulness and sleepiness is a more complex story.

Certain serotonergic neurons fire more during waking while others show different patterns.

Adenosine builds up over the course of the waking period, as it is a byproduct of metabolism. Its concentration variation can be a proxy for the homeostatic sleep drive.

The neurons in the median preoptic nucleus of the hypothalamus and the ventrolateral preoptic area of the hypothalamus (VLPO) release GABA at command of the suprachiasmatic nuclease when it is time to sleep. The immune system is also activated by lack of sleep and cytokines essentially function as sleep promoters in the brain. Melatonin, varying in concentration with the circadian cycle, promotes sleep.

Further study of neurotransmitters and how they work will ly lead to treatments of nervous system disorders, depression and possibly even diseases Alzheimer’s. Research on neurotransmitters is illuminating the causes of and possible treatments for chemical addictions. There are probably neurotransmitters involved in sleep that are yet undiscovered.

Additional Resources:

Source: https://www.tuck.com/neurotransmitters/

Sleep/Wake Cycles

How Brain Health & Neurotransmitters Affect Sleep

Sometimes you drift off to sleep easily. Other times you toss and turn for hours before you slip into a fitful sleep. After lunch you may be dragging. Later, your energy levels soar just in time for bed.

How and when you feel sleepy has to do with your sleep/wake cycles. These cycles are triggered by chemicals in the brain.

Brain chemicals and sleep

Chemicals called neurotransmitters send messages to different nerve cells in the brain. Nerve cells in the brainstem release neurotransmitters. These include norepinephrine, histamine, and serotonin. Neurotransmitters act on parts of the brain to keep it alert and working well while you are awake.

Other nerve cells stop the messages that tell you to stay awake. This causes you to feel sleepy. One chemical involved in that process is called adenosine. Caffeine promotes wakefulness by blocking the receptors to adenosine. Adenosine seems to work by slowly building up in your blood when you are awake. This makes you drowsy. While you sleep, the chemical slowly dissipates.

Sleep processes

Two body processes control sleeping and waking periods. These are called sleep/wake homeostasis and the circadian biological clock.

With sleep/wake homeostasis, the longer you are awake, the greater your body senses the need to sleep. If this process alone was in control of your sleep/wake cycles, in theory you would have the most energy when you woke up in the morning. And you would be tired and ready for sleep at the end of the day.

But your circadian biological clock causes highs and lows of sleepiness and wakefulness throughout the day. Typically, most adults feel the sleepiest between 2 a.m. and 4 a.m., and also between 1 p.m. and 3 p.m. Getting plenty of regular sleep each night can help to balance out these sleepy lows.

Your body’s internal clock is controlled by an area of the brain called the SCN (suprachiasmatic nucleus). The SCN is located in the hypothalamus. The SCN is sensitive to signals of dark and light. The optic nerve in your eyes senses the morning light.

Then the SCN triggers the release of cortisol and other hormones to help you wake up. But when darkness comes at night, the SCN sends messages to the pineal gland. This gland triggers the release of the chemical melatonin.

Melatonin makes you feel sleepy and ready for bed.

Neurotransmitters and your sleep

Some neurotransmitters help your body recharge while you sleep. They can even help you to remember things that you learned, heard, or saw while you were awake.

The neurotransmitter acetylcholine is at its strongest both during REM (rapid eye movement) sleep and while you are awake. It seems to help your brain keep information gathered while you are awake. It then sets that information as you sleep.

So if you study or learn new information in the hours before bed, “sleeping on it” can help you remember it.

Other neurotransmitters may work against you as you sleep. Abnormalities with the neurotransmitter dopamine may trigger sleep disorders such as restless legs syndrome.

Even losing just 1 hour of sleep over a few days can have an effect. It can lead to a decrease in performance, mood, and thinking. Getting regular, adequate amounts of sleep is important. It can help you feel awake and refreshed during the day. It can also help you feel relaxed and sleepy at night. This helps make you ready for a long, restful night of sleep. 

Source: https://www.hopkinsmedicine.org/health/conditions-and-diseases/sleepwake-cycles

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