How Light, Sleep, and Stress Shape Your Brain and Body: The Orexin Eye Prism

The Brain’s Hidden Conductor: How Light Controls Sleep, Energy, and Emotion - The Orexin Eye Prism - The Hypocretinergic (Orexin) System and G-Proteins

G-Proteins: G-proteins serve as crucial intermediaries in cell signalling, transmitting signals from cell surface receptors to intracellular pathways. They facilitate the activation of downstream effectors, regulating various cellular processes and mediating responses to external stimuli, hormones, neurotransmitters, and other signalling molecules.

Melanopsin forms a functional photopigment capable of catalysing (speeding up) G-protein activation in a light-dependent manner. Melanopsin responds to light stimuli and initiates signalling pathways through the activation of G-proteins, leading to various physiological and behavioral responses, such as regulating circadian rhythm and pupillary reflex. This G-receptor needs docosahexaenoic acid (DHA) to function optimally. It is the melanopsin iPRGC’s that generate melatonin rhythms in the pineal gland.

G-proteins are involved in a wide range of cellular processes, including neurotransmission, hormone signaling, sensory perception, cell growth and differentiation, and immune responses. They are critical for mediating and amplifying signals from cell surface receptors and relaying them to various intracellular pathways to initiate appropriate cellular responses.

Guanosine triphosphate (GTP) – Protein Synthesis and G-Protein Signaling

GTP, participates in energy transfer reactions specifically associated with processes like protein synthesis and G-protein signaling. GTP is involved in protein synthesis and the process of translation. During translation, GTP binds to elongation factors and serves as an energy source to facilitate the addition of amino acids to the growing polypeptide chain. GTP hydrolysis releases the energy required for the elongation of the protein chain. GTP is a critical component in G-protein signalling, where GTP binding to G-proteins triggers downstream signalling cascades

·       Dysregulation of G-protein signalling has been implicated in various neurodegenerative diseases. Mutations or abnormalities in proteins involved in G-protein signalling pathways can disrupt normal cellular signalling and contribute to the development and progression of neurodegenerative disorders.

·       For example, dysfunction of G-protein-coupled receptors (GPCRs) and their associated G-proteins has been observed in diseases like Parkinson's disease and Alzheimer's disease. Altered signalling through GPCRs can affect crucial processes, such as neurotransmitter release, synaptic plasticity, and neuronal survival, which are vital for maintaining proper neuronal function.

·       Additionally, abnormalities in G-protein signalling components can lead to increased inflammation, oxidative stress, and impaired cellular processes, all of which are implicated in neurodegeneration.

·       Oxytocin and G-proteins

OXTR or Oxytocin Receptor encodes a protein that belongs to the G-protein coupled receptor family and acts as a receptor for oxytocin. Oxytocin receptors regulate a variety of different behaviours such as stress, anxiety, social recognition, bonding, and maternal behaviour.

Variants in this gene can lead to a higher sensitivity to stress and conduct disorders.

The Hypocretinergic System (Orexin/Hypocretin System)

The purpose of the hypocretinergic system, also known as the Orexin system, is to regulate sleep-wake cycles, maintain wakefulness, and promote alertness during the day, while also influencing appetite, energy homeostasis, reward mechanisms, and stress responses in the body. Part of the CNS.

References: https://www.health.harvard.edu/staying-healthy/blue-light-has-a-dark-side

Light and Neuroendocrine Function (Orexin Ghrelin and Leptin)

Light exposure has a significant impact on neuroendocrine function, including the regulation of hormones such as ghrelin and leptin, which are critical in energy homeostasis and feeding behavior. The light environment influences neuroendocrine function through endocrine systems that display 24-hour variations in activity, aligned to daily changes in external illumination. These light-dependent signals are relayed via the suprachiasmatic nucleus of the hypothalamus (SCN), which plays a key role in this process.

Leptin, an adipocyte-derived hormone, is involved in reducing food intake by regulating the activity of neurons in the arcuate nucleus of the hypothalamus. Circadian rhythms of leptin are regulated primarily by the liver circadian clock which pays attention to the orbital angular momentum (OAM) energy and information signals within the electrons in the food we consume (food intake), and acute sleep deprivation has been shown to reduce blood concentrations of leptin, potentially facilitating weight gain if persisting over extended periods of sleep loss. Light in the eye and skin has not yet shown a primary role in regulating leptin but it may be discovered to be more important for tuning this vital system in the coming years.

Ghrelin, the only known orexigenic hormone from the periphery, stimulates food intake. Plasma ghrelin levels are enhanced under conditions of physiological stress and have been suggested to play an important role in stress-induced food reward behavior.[5] Acute sleep deprivation has been shown to increase blood concentrations of ghrelin, which may also contribute to weight gain if persisting over extended periods of sleep loss.

In summary, light exposure, through its influence on the SCN, plays a significant role in the regulation of ghrelin and leptin, hormones critical to energy balance and feeding behavior. Disruptions in light exposure, such as through sleep deprivation, can lead to alterations in these hormones, potentially contributing to metabolic disorders such as obesity.

Cite: https://pubmed.ncbi.nlm.nih.gov/31394505

Production and release of Orexin-A and Orexin-B from the Hypothalamus

Orexin system plays a significant role in regulating various physiological processes, including:

• Sleep-Wake Cycle Regulation: Orexin neurons are involved in promoting wakefulness and regulating the sleep-wake cycle. They help keep individuals awake and alert during the day and are inactive during sleep.
• Appetite and Feeding Behavior: The orexin system also influences appetite and feeding behavior. Orexin neurons stimulate hunger and food-seeking behavior.
• Energy Homeostasis: Orexin is involved in the regulation of energy balance and metabolism.
• Emotional Regulation: The orexin system plays a role in emotional regulation and may be linked to stress responses and emotional states.
• Reward and Addiction: Some research suggests that orexin may be involved in the brain's reward system and could play a role in addiction and reward-seeking behaviors.
• The orexin system is interconnected with other brain regions and neurochemical systems, and disruptions in this system have been associated with various conditions, including narcolepsy (a sleep disorder), obesity, diabetes (type 1-3), and mood disorders.

Sleep-wake cycles, appetite and feeding behavior, energy homeostasis, reward mechanisms, and arousal. It acts as a link between different brain regions and helps integrate information related to these functions

Orexin neurons receive inputs from ipRGCs, and other brain regions involved in circadian rhythm regulation.

Orexin-A has been shown to increase the excitability of ipRGCs like Melanopsin, making them more responsive to light stimuli. This activation of ipRGCs by Orexin-A can enhance the transmission of light information to the brain regions involved in regulating circadian rhythm.

What can upregulate Orexin-A and Orexin-B to make us more light sensitive?

1.       Hypocretin gene expression: The transcription and expression of the hypocretin/orexin genes in the neurons of the hypothalamus can be influenced by various factors. Research suggests that transcription factors like cAMP response element-binding protein (CREB), nerve growth factor-inducible protein A (NGFI-A), and clock genes may be involved in regulating hypocretin gene expression.

2.       Arousal and wakefulness: Orexin-A and Orexin-B are known to promote wakefulness and arousal. Therefore, states or factors that enhance arousal, such as stress, physical activity, and novel or rewarding stimuli, can increase the release of these neuropeptides.

3.       Light exposure: Light exposure, particularly blue light, can modulate the expression and release of Orexin-A and Orexin-B. The ipRGCs in the retina, which detect light, project to the hypothalamus and provide input to Orexin neurons. Activation of ipRGCs by light can stimulate Orexin release, contributing to the regulation of circadian rhythm and wakefulness.

4.       Food intake and fasting: Orexin neurons are involved in regulating appetite and feeding behavior. Studies have shown that food intake and fasting can modulate Orexin-A and Orexin-B expression. Feeding-related signals, such as ghrelin (a hunger hormone) and leptin (a satiety hormone), can influence the activity of Orexin neurons and the release of Orexin peptides.

5.       Stress and emotional states: Stressful situations and emotional states can impact the Orexin system. Stress hormones like cortisol and corticotropin-releasing hormone (CRH) can affect Orexin neurons and increase Orexin release. Orexin neurons also receive input from brain regions involved in emotional processing, suggesting a role in regulating emotional states.

When Orexin-A or Orexin-B binds to their respective G-protein coupled receptors (OX1R and OX2R), it triggers a series of intracellular events mediated by G-proteins. Here's a general overview of the process:

1. Binding and receptor activation: Orexin-A or Orexin-B binds to the OX1R or OX2R receptor on the cell surface. This binding induces a conformational change in the receptor, leading to its activation.

2. G-protein coupling: Activated OX1R and OX2R receptors interact with G-proteins, specifically Gq/11 proteins. This interaction facilitates the exchange of GDP (guanosine diphosphate) bound to the G-protein with GTP (guanosine triphosphate), causing the G-protein to become activated.

3. Effector activation: Activated G-proteins dissociate into Gα (alpha) and Gβγ (beta-gamma) subunits. These subunits can then modulate various effector molecules, such as enzymes or ion channels. For example, the Gαq/11 subunit can activate phospholipase C (PLC), leading to the production of inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 triggers calcium release from intracellular stores, while DAG activates protein kinase C (PKC), initiating downstream signaling events.

4. Cellular response: The activation of effector molecules and subsequent intracellular signaling events triggered by G-proteins lead to various cellular responses. In the context of the Orexin system, these responses can include the regulation of neuronal excitability, neurotransmitter release, and modulation of intracellular calcium levels, among others.

Overall, the Orexin system utilizes G-protein coupled receptors and their associated G-proteins to transmit signals from Orexin peptides to intracellular pathways, ultimately resulting in specific cellular responses.

Food and Orexin:

The advice to “eat more healthy whole grains” has got to be the crime of the century. The second biggest crime of the century is the advice to cut down on “cholesterol” (fat) intake.

“Healthy” whole grains are responsible for initiating all of the diseases of modern man. Every organ in the body, including the hypothalamus, is controlled by nerve transduction boundaries. Zonulin makes transduction boundaries permeable to gluten and casein opioids. These boundaries are normally protected by the blood brain barrier (BBB).

The blood brain barrier is not really a barrier at all. It is mostly controlled by the fact that nerves operate in a hydrophobic environment …. a fat amalgam which controls phospholipid-rich nerve membranes. Control and restoration of these transduction boundaries requires replenishment by ingested fats, and proper cholesterol manufacture by the liver. Protection of these transduction boundaries requires ……adenosine. And adenosine is an essential protein. It is mostly a product of complete digestion of proteins in the gut. Eating grassy grains arrests digestion of plant proteins and dumps them into the blood before digestion can produce adequate adenosine. The zonulin and opioid assault on cholesterol-starved nerve transduction boundaries is aided by a shortage of adenosine and cholesterol.

Destruction of circadian rhythm is a two-prong assault. Deterioration of hypothalamus transduction boundaries allows compromise of the orexin/hypocretin system. That’s a BIG problem. The body has three states …. exert, rest and eat. The orexin system has tendrils directly into the transduction control nerves of every organ. Orexin control impulses toggle organs like a symphony conductor toggles instrument sections. Once the hypothalamus orexin center has been compromised, organs lose the capability to sleep and wake on demand.

The wheat-compromised immune system gets confused. It begins, as you said, different patterns of cytokine release. One of the immune system targets becomes ingested polyphenol dyes like lutein. Lutein has an affinity for retinal nerves. Like vitamin A, lutein coats the retina, blocking out blue light. Blue light in the retina is responsible for setting the circadian clocks which control our pineal glands. Our wheat-compromised immune systems attack lutein and attack the retina. The attack destroys eyesight and destroys the pineal gland control nerve’s ability to tell day from night.

Computation in the nervous system often relies on the integration of signals from parallel circuits with different functional properties. Correlated noise in these inputs can, in principle, have diverse and dramatic effects on the reliability of the resulting computations. Orexin neurons in the brain have this effect on the decentralized neural networks that control the circadian mechanism of man.

Such theoretical predictions have rarely been tested experimentally because of a scarcity of preparations that permit measurement of both covariation of a neuron’s input signals and the effect of manipulating such covariation on a cell’s output. Scientists have now introduced a new method to measure the covariation of the excitatory and inhibitory inputs a cell receives. This method revealed a strongly correlated noise in the inputs to two types of retinal ganglion cells. Eliminating correlated noise without changing other input properties substantially decreased the accuracy with which a cell’s spike outputs encoded light inputs.

Orexins are the prism in your retina that is the conductor of controlling your biological life. Thus, covariation of excitatory and inhibitory inputs is a critical determinant of the reliability of neural coding and computation in circadian signalling. Orexins are the key prism of the retina that controls the quantum coherence of water and builds the stage life dances upon.

The retina is a prism. It has photoreceptors for color vision, it has melanopsin for SCN function, it has orexin neurons, it has neuropsin, and it has Müller cells that are optical fibres to refract the light.

Mueller Cells - Müller cells are radial glial cells spanning the entire retinal thickness. Muller cells act as astrocytes do in forming the blood-brain barrier. Astrocytes make up the blood-brain barrier. They release vitamin C to stress to alter metabolism to help NAD+ recycle faster to create ATP. In the retina, Muller cells do the same thing for the neurons of the retina. The glial Müller cells in the retina, regulate the glutamate cycle to prevent damage in oxidative stress conditions of the photoreceptors. Müller cells have an extended funnel shape, a higher refractive index than their surrounding tissue, and are oriented along the direction of light propagation in the eye. Müller cells provide trophic and anti-oxidative support for photoreceptors and neurons and regulate the tightness of the blood-retinal barrier.

Cite: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727383/

I believe IR-A light has a massive effect on cytochrome c oxidase to help regenerate damaged retina. I believe that mitochondria in the Muller glial cells provide a massive source of red photons that are absorbed by the copper subunit of the terminal enzyme, cytochrome c oxidase (CCO). PBM likely affects other parts of the electron transport chains of mitochondria like the Q-cycle as well. I believe the light absorbed by CCO enhances the ability of the mitochondria to catalyze the reduction of oxygen to produce ATP more efficiently. It also augments the creation of water, which becomes a source of delocalized electrons and protons that can be used to regenerate damaged parts of the retina.

As CCO redox activity increases from PBM therapy, oxygen consumption also increases in the retina, leading to a rise in the rate of oxidative phosphorylation as well as cellular oxygen metabolism. Since neurons in the retina have an increased reliance on mitochondrial oxygen metabolism compared to most other cell types, PBM has already been shown to affect neuronal functions significantly by raising ATP production. UV light seems like it would limit regeneration by this mechanism. But cytochrome c oxidase uses the amount of UV/IR stimulus by not releasing partly reduced intermediates by partly holding O2 tightly between iron and copper ions. If this protection was not given by nature, only partial reduction of O2 is generated. This creates the ROS signal.

Traumatic stress of any type can elevate glutamate to abnormally high levels in the brain/retina. Light stress increases glutamate via the activation of orexin A in the retina. A brain injury or stroke causes glutamate to flood the injured area.

Cite: https://link.springer.com/article/10.1007/s10571-020-01016-9

PBM likely increases the uptake of glutamate, helping the Müller cells to protect the retina. They are more directly involved in the regulation of the synaptic activity in the inner retina. They help organize the chaos that light creates in the retina. Orexins seem evolved to deal with the chaos the sun creates and not any man-made light. Man-made light seems to unleash orexin A so that the PVN is chronically turned on to give us a syndrome that mimics adrenal fatigue. It should not surprise you because light stress stimulates orexin A and this activates the PVN. This also releases glutamate and an excessive amount of Vitamin C. When Vitamin C is exhausted none of the catecholamine molecules associated with adrenal fatigue can be made. This is why adrenal fatigue is not an adrenal disease. It is a disease of the eyes, orexin, and the PVN due to excessive glutamate release and excessive use of Vitamin C so that dopamine, epinephrine, and noradrenaline can’t be made.

Cite: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725212/

The light is broken down into its parts to impart information to the retina. In this way, Perception is a prism, and the retina is like shot silk, the quality of information it imparts depends on the quality and quantity where the light hits.

Counterintuitively, the retina of the vertebrate eye is inverted with respect to its optical function and light must pass through several tissue layers before reaching the light-detecting photoreceptor cells. This is because the eye needs to slow light down and send the light to areas inside in a stepwise fashion.

In mammals and humans, the extent of spontaneous repair after retina injury or disease is either non-existent or extremely limited (Karl and Reh, 2010). Rather than regenerate, damaged mammalian retinas commonly undergo reactive gliosis and scar formation (Bringmann et al., 2006).

Muller cells were the key to understanding how to regenerate damaged retinal tissues.

The information the retina creates is stored electromagnetically in coherent domains of water in cells like the Muller glia and in the CSF that surrounds the key areas of the brain that interact with the environment. CSF is made by the choroid plexus in the brain. CSF is an ultrafiltrate of the blood.

Orexin Neurons - Orexins are hypothalamic neuropeptides that were initially identified in the rat brain as endogenous ligands for a (previously) orphan G-protein-coupled receptor (GPCR). They are the rare neurons in the entire human brain. Scarcity creates its value to signalling when it comes to light. Light strikes things and changes them in ways our retina cannot sense. This makes light the most powerful change stimulus behind our evolutionary adaptation. They are multitasking peptides involved in many physiological functions, including regulation of feeding behaviour, wakefulness and autonomic/neuroendocrine functions, and sleep/wakefulness states in mammals. There are two isopeptides of orexin, orexin A and orexin B, which are produced from a common precursor peptide, pre-pro-orexin. Orexin neurons widely project to all regions of the brain including the hypothalamus (de Lecea et al., 1998; Peyron et al., 1998), thalamus, cortex, brain stem, and spinal cord (van den Pol, 1999). There aren’t many of them, but their impact on water chemistry in us defines a non-linear stimulus where a small stimulus leads to a massive change. The lengths and structure of orexins suggested that orexin B is the ancestral form of the orexin neuropeptide. In mammals, orexins bind to two subtypes of GPCRs, i.e., orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R). UV and red/IR light operate on these two orexins from sunlight. I believe that orexin-A works best with UV light signalling and Orexin-B is optimized by red/infrared light in our tissues. Thus, Orexin B are proteins that absorb the slowest form of light we are designed to operate with (Infrared) in tissue to maximize the fidelity of the signal. Orexin A neurons strongly excite various brain nuclei (via UV light stimulus) with important roles in wakefulness including the dopamine, norepinephrine, histamine (all made from aromatic amino acids), and acetylcholine systems, and appear to play an important role in stabilizing wakefulness and sleep (adenosine), Adenosine is activated by IR-A light. The sleep-promoting action of adenosine can be reversed by orexin A applied to the lateral hypothalamus, by exciting glutamatergic input to orexin neurons via the action of orexin receptor 1. I believe it is the ultraweak release of UV light that disrupts the S-S bond of Orexin-A that cause sympathetic outflow to increase. This leads to REM sleep disorders such as narcolepsy.

The discovery that an orexin receptor mutation causes the sleep disorder canine narcolepsy in Doberman Pinschers subsequently indicated a major role for this system in sleep regulation. Narcolepsy is a REM sleep disorder. Genetic knockout mice lacking the gene for orexin were also reported to exhibit narcolepsy. In humans, narcolepsy is associated with a specific variant of the human leukocyte antigen (HLA) complex. A lack of either red light or UV light is how narcolepsy begins. It begins with poor light signalling in the prism of the retina. Light changes the charge density of the retina. The proof is found in genome-wide analysis studies that show that, in addition to the HLA variant, people with narcolepsy also exhibit a specific genetic mutation in the T-cell receptor alpha locus. In conjunction, there are genetic anomalies that cause the immune system to attack and kill the critical orexin neurons. Once they are destroyed, they do not come back. Hence the absence of orexin-producing neurons in people with narcolepsy appears to be the result of an autoimmune disorder. We also see these effects in the hydrogen bonding networks of water in cells, in the blood, and in the CSF.

The structures of orexins, as well as orexin genes, are highly conserved throughout mammalian species, suggesting strong evolutionary pressure has maintained these structures for approximately 650 million of years. In this way, orexins are like DHA they haven’t changed in hundreds of millions of years of vertebrate evolution. Orexin A is a 33-amino-acid peptide with an N-terminal pyroglutamyl residue, two intrachain disulfide bonds, and C-terminal amidation (removes the charge form the C-terminus of a peptide). Strikingly, this structure is completely conserved among all mammalian species so far identified in the literature. This means orexin A is the same in humans, gorillas, rats, mice, cows, pigs, sheep, dogs, seals, and dolphins. Very few proteins have been found to have this long-term evolutionary lineage.

There are only 50,000–80,000 orexin-producing neurons in the human brain, located predominantly in the perifornical area and lateral hypothalamus. The hypothalamus sits adjacent to the third ventricle which is filled with CSF. CSF is 99.8% water created by mitochondria. The central retinal pathways in the retina of all mammals contain orexin neurons that project to the areas of the brain adjacent to CSF pathways. Orexin-producing neurons (orexin neurons), in the lateral hypothalamus, receive input from the forebrain structures including the extended amygdala and nucleus accumbens (NAc), which are implicated in the processing of emotion and motivation, and send output to brain stem regions, which are implicated in the regulation of wakefulness. Because sleep was our primordial state, and we evolved wakefulness. I believe the orexin neurons were key in this transition. Orexin made water more quantum coherent so more energy could be harvested to allow wakefulness to emerge. Orexin neurons play an important role as a link between emotional states and wakefulness states. Any acute stress activates orexin neurons, and this includes modern light stress. This is why I have believed adrenal fatigue is a disease of the periventricular nucleus. I believe orexins are the fuse that begins the process.

Light transmission via the retina interacts with the amacrine cell level in the retina which in turn activates both orexin systems. The orexin systems modulate the stress response in mammals. The orexin system was initially suggested to be primarily involved in the stimulation of food intake, based on the finding that central administration of orexin-A and -B increased food intake. In addition, they stimulate wakefulness, regulate energy expenditure, and modulate the visceral function and brown fat activation. Many studies support that the orexin neurons regulate brown adipose tissue (BAT) activity via the sympathetic nervous system to enhance energy expenditure.

The photosensitivity of protein-bound cysteine residues has been shown to depend on the redox state of the microenvironment. References below:

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373466/#koudelka-and-augenstein-1968
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373466/#risi-etal-1967
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373466/#fiore-and-dose-1965
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373466/#augenstein-and-riley-1964
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373466/#augenstein-and-ghiron-1961
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373466/#augenstein-and-ghiron-1961

Note that orexin has one tyrosine adjacent to its S-S bond. All cells release ultra-weak UV light. Vertebrate eukaryotes tend to release less ultraweak UV light unless the redox state is low. When it is low eukaryotes release significantly more ultraweak UV. The excessive ultraweak UV light then disrupts the S-S of orexin A and this changes the tertiary and quaternary protein folding of orexin and alters its physiologic signalling optically. These photodynamic reactions allow for a temporally and spatially controlled and reversible modification of the surface of orexin A and, hence, can be used to produce functional interfaces that change signalling.

• https://www.sciencedaily.com/releases/2017/01/170116091638.htm

It has been reported that the UV illumination of Tryptophan and Tyrosine residues gives rise to delocalized electrons. UV light can also liberate hydrogen from aromatic amino acids into the hydration shell. The H-atom ejection from these amino acids was written about decades ago. (Vladimirov et al. 1970; Feitelson 1971). Cystine residues have a clear preference for aromatic residues as spatial neighbours. The role of the hydrated electron in photo-reduction of cystine in the presence of indole (melatonin is an indole) led to the proposal of a possible mechanism behind this phenomenon over 50 years ago (Grossweiner and Usui 1970). These papers show what orexins are really doing. The liberation of these electrons and protons is what changes the hydrogen bonding network to become coherent domains. Orexins are the gatekeepers that force water to take on a hexagonal form to become quantum coherent in the brain. 

 

 

Orexin connection to Melatonin

Melatonin and dopamine are known to be critical in regenerating all human photoreceptors.

Melatonin has two receptors, MT1 and MT2.

The MT1 receptor is involved in the regulation of the circadian rhythm. The MT1 receptor is in the locus coeruleus and lateral hypothalamus where REM areas exist. This is the same area where orexin neurons project to. When these orexin neurons are destroyed there, we also see a REM sleep disorder develop called narcolepsy. People with narcolepsy frequently enter REM sleep rapidly with sleep onset. This usually happens within 15 minutes of falling asleep day or night. Also, muscle weakness or dream activity that is associated with REM sleep can occur during wakefulness or be absent during sleep. REM normally occurs in short periods and is characterized by a decrease in muscle tone and is associated with profound sympathetic activation (PVN), including increased heart rate, breathing, blood pressure, and temperature.

The MT2 receptor does not regulate the circadian rhythm MT2 receptors are located in the reticular thalamus which is the non-REM sleep area. Non-REM sleep disorders are also called arousal disorders. Non-REM parasomnias involve physical and verbal activity. You are not completely awake or aware during these events, are not responsive to others’ attempts to interact with you, and usually don’t remember or only partially remember the event the next day.

Remember, there are a lot of photoreceptors in the eye like melanopsin, melatonin, neuropsin, B12, dopamine, melanin, cytochrome c oxidase, nitric oxide, and heme proteins like catalase in RBCs etc. 

The periventricular nucleus controls our sympathetic response by how it reacts to the orexin signal from the central retinal pathways. Moreover, the choroid plexus (CP) of the brain that creates CSF has recently been implicated in the regulation of circadian rhythmicity and therefore, it is now recognized that the functions of the CP cannot be limited to those listed in textbooks. There is a strong circadian influence over the sleep-wake cycle and orexinergic signalling. Considering that the sleep-wake cycle modulates additional homeostatic processes such as amyloid-β and glymphatic clearance, the hydrogen bonding networks in the Choroid Plexus may also have a significant influence on the activity of these functions. The key to the orexin prism is found in its 33–amino–acid peptide sequence that has two intrachain disulfide bridges formed by four cysteine residues (C6–C12 and C7–C14). The S-S bond in orexin-A induces proteins to misfold due to the effect of UV light on this bond. Brains with neurodegeneration all have low redox states and this means they will release a lot more ultra-weak UV light. This light will destroy orexin-A and lead to protein misfolding at a log rate. As this light stress develops, glutamate rises, and the BBB becomes leaky. The process progresses and gets worse. The sympathetic system outflow of the stress stimulus begins in the paraventricular nucleus (PVN). The vagus nerve is the major outflow tract that is the calming portion of the ANS and antagonizes the PVN to lower the stress response. It has an amazing effect on the hexagonal prisms in CSF in the 4th ventricle. This signal can be turned on and off by the light that comes through the prism of our retina. This is why the light you allow is critical in signalling in how it changes hydrogen bonding in water. Cysteine has something in common with orexin. Cysteine is the rarest amino acid and being rare means, it increases signal fidelity. Eliminating correlated noise without changing other input properties substantially decreased the accuracy with which a cell’s spike outputs encoded light inputs in retinal ganglion cells. Thus, covariation of excitatory and inhibitory inputs in the orexin system can be a critical determinant of the reliability of neural coding and computation in its target in the brain. Orexin input to brain regions important for arousal, such as the locus coeruleus, help to regulate the response to a stressor (Hagan et al., 1999). Moreover, orexin-containing nerve terminals project to stress-sensitive centres such as the amygdala and bed nucleus of the stria terminalis (Date et al.,1999). Orexin neurons also project to the paraventricular nucleus of the hypothalamus (PVN) (Winsky-Sommerer et al., 2004), where neurons expressing corticotropin-releasing hormone (CRH = cortisol) initiate the Hypothalamic Pituitary Adrenal (HPA) Axis. This forms half of the circadian mechanism of cortisol and melatonin. orexin neurons densely project to the paraventricular nucleus of the thalamus (PVT) (Kirouac et al., 2005), which plays a role in regulating neuroendocrine and behavioral adaptations to severe or chronic stress (Hsu et al.,2014). Specifically, orexins may influence gene expression of the CRH type 1 receptor (CRH1R) in the paraventricular nucleus of the thalamus (Heydendael et al., 2012, 2011), and this brain region may then regulate the HPA axis via multisynaptic pathways through the BNST to the PVN. The orexin neuropeptides orexin A and orexin B interact with noradrenergic, cholinergic, serotonergic, histaminergic, and dopaminergic systems in the brain, in addition to the HPA axis (Sutcliffe and de Lecea, 2000). Thus, orexins have the potential to regulate the stress response through actions at multiple projection sites. All mental disorders likely begin with orexin dysfunction.

CSF-contacting neurons are present in all vertebrates and are located mainly in the hypothalamic area and the spinal cord. The hypothalamus lies below the hypothalamic sulcus separating it from the thalamus above. Like the thalamus, a thin vertical space filled with CSF called the 3rd ventricle is positioned midline between the two halves of the hypothalamus thalamus. The blood-brain barrier is absent around the vagal vom

iting center of the 4th ventricle so that it can monitor the blood for changes. The blood-brain barrier is also absent around the various areas in the hypothalamus where orexin targets land their signalling.

The stimulus of light from the orexin prisms in our retina changes the CSF’s hydrogen bonding networks to a hexagonal arrangement that allows for another prism to be built in water that stores electromagnetic information to make the brain quantum coherent. Full-spectrum sunlight reaching the brain creates more coherent domains in water. Normally water is only 40% quantum coherent. From here on out you should realize that coherent domains should be regarded as long-range ensembles of electrons and protons of exclusion zones inside the water that has the superconductive ability at room temperature. This type of water is a plasma filled with electrons and protons. Biological water has unique characteristics that make life possible. Orexins have the biggest prism effect of making water the stage on which life performs on.

Cites:

1. https://www.pnas.org/doi/10.1073/pnas.0611180104
2. Myung J, Schmal C, Hong S, et al. The choroid plexus is an important circadian clock component. Nat Commun2018; 9: 1–13.
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