What is the most abundant neurotransmitter in the human brain?
Glutamic acid
Glutamate is also a neurotransmitter (see below), which makes it one of the most abundant molecules in the brain. Malignant brain tumors known as glioma or glioblastoma exploit this phenomenon by using glutamate as an energy source, especially when these tumors become more dependent on glutamate due to mutations in the gene "IDH1".
Benzodiazepine dependence
Withdrawal symptoms are a normal response in individuals having chronically used benzodiazepines, and an adverse effect and result of drug tolerance. Symptoms typically emerge when dosage of the drug is reduced. GABA is the second-most-common neurotransmitter in the central nervous system (the most common being glutamate) and by far the most abundant inhibitory neurotransmitter; roughly one-quarter to one-third of synapses use GABA. The use of benzodiazepines has a profound effect on almost every aspect of brain and body function, either directly or indirectly.
Glutamic acid
Glutamate is the most abundant excitatory neurotransmitter in the vertebrate nervous system. At chemical synapses, glutamate is stored in vesicles. Nerve impulses trigger release of glutamate from the presynaptic cell. Glutamate acts on ionotropic and metabotropic (G-protein coupled) receptors. In the opposing postsynaptic cell, glutamate receptors, such as the NMDA receptor or the AMPA receptor, bind glutamate and are activated. Because of its role in synaptic plasticity, glutamate is involved in cognitive functions such as learning and memory in the brain. The form of plasticity known as long-term potentiation takes place at glutamatergic synapses in the hippocampus, neocortex, and other parts of the brain. Glutamate works not only as a point-to-point transmitter, but also through spill-over synaptic crosstalk between synapses in which summation of glutamate released from a neighboring synapse creates extrasynaptic signaling/volume transmission. In addition, glutamate plays important roles in the regulation of growth cones and synaptogenesis during brain development as originally described by Mark Mattson.
Neuropharmacology
The serotonin neurotransmitter has the ability to mediate synaptic transmission through either GPCR's or LGIC receptors. Depending on what part of the brain region serotonin is being acted upon, will depend on whether the output is either increasing or decreasing post-synaptic responses. The most popular and widely used drugs in the regulation of serotonin during depression are known as SSRIs or selective serotonin reuptake inhibitors. These drugs inhibit the transport of serotonin back into the pre-synaptic neuron, leaving more serotonin in the synaptic gap to be used.
Glutamate carboxypeptidase II
Glutamate is the “primary excitatory neurotransmitter in the human nervous system”, participating in a multitude of brain functions. Over-stimulation and -activation of glutamate receptors as well as “disturbances in the cellular mechanisms that protect against the adverse consequences of physiological glutamate receptor activation” have been known to cause neuron damage and death, which have been associated with multiple neurological diseases.
Animal model of schizophrenia
Glutamate is the most abundant excitatory neurotransmitter in vertebrate nervous systems. Evidence for the involvement of glutamate in schizophrenia includes analogous symptoms which are produced by glutamate NMDA receptor antagonists such as phencyclidine (PCP) and ketamine. PCP is a non-competitive NMDA receptor antagonist which produces hallucinations and delusions in normal subjects. In rat models, disturbed cognition, deficits in social interaction, locomotor anomalies, and prepulse inhibition deficits are seen on acute administration of PCP. Evidence that persistent PCP use and abuse in humans results in lasting deficits beyond the period of treatment has led to the suggestion that this regime in rodents may be a more accurate model of schizophrenia than acute administration. A number of protocols for chronic PCP animal models have been developed, with different effects. The effects of some, but not all protocols can be reversed by treatment with antipsychotics. In a primate model, PCP was found to induce cognitive impairments which were reversed with clozapine.
Neurotransmitter
A neurotransmitter can influence the function of a neuron through a remarkable number of mechanisms. In its direct actions in influencing a neuron's electrical excitability, however, a neurotransmitter acts in only one of two ways: excitatory or inhibitory. A neurotransmitter influences trans-membrane ion flow either to increase (excitatory) or to decrease (inhibitory) the probability that the cell with which it comes in contact will produce an action potential. Thus, despite the wide variety of synapses, they all convey messages of only these two types, and they are labeled as such. Type I synapses are excitatory in their actions, whereas type II synapses are inhibitory. Each type has a different appearance and is located on different parts of the neurons under its influence. Each neuron receives thousands of excitatory and inhibitory signals every second.
Glutamate (neurotransmitter)
Glutamate is a major constituent of a wide variety of proteins; consequently it is one of the most abundant amino acids in the human body. Under ordinary conditions enough is obtained from the diet that there is no need for any to be synthesized. Nevertheless, glutamate is formally classified as a non-essential amino acid, because it can be synthesized from alpha-Ketoglutaric acid, which is produced as part of the citric acid cycle by a series of reactions whose starting point is citrate. Glutamate cannot cross the blood-brain barrier unassisted, but it is actively transported into the nervous system by a high affinity transport system, which maintains its concentration in brain fluids at a fairly constant level.
Diabetic hypoglycemia
If a person has frequent episodes of hypoglycemia (even mild ones), the brain becomes "used to" the low glucose and no longer signals for epinephrine to be released during such times. More specifically, there are glucose transporters located in the brain cells (neurons). These transporters increase in number in response to repeated hypoglycemia (this permits the brain to receive a steady supply of glucose even during hypoglycemia). As a result, what was once the hypoglycemic threshold for the brain to signal epinephrine release becomes lower. Epinephrine is not released, if at all, until the blood glucose level has dropped to even lower levels. Clinically, the result is hypoglycemic unawareness.
Neuropeptide S
Neuropeptide S (NPS) is a neuropeptide found in human and mammalian brain, mainly produced by neurons in the amygdala and between Barrington's nucleus and the locus coeruleus, although NPS-responsive neurons extend projections into many other brain areas. NPS binds specifically to a G protein-coupled receptor, NPSR. Animal studies show that NPS suppresses anxiety and appetite, induces wakefulness and hyperactivity, including hyper-sexuality, and plays a significant role in the extinction of conditioned fear. It has also been shown to significantly enhance dopamine activity in the mesolimbic pathway, and inhibits motility and increases permeability in neurocrine fashion acting through NO in the myenteric plexus in rats and humans.
Biochemistry of Alzheimer's disease
The human brain is one of the most metabolically active organs in the body and metabolizes a large amount of glucose to produce cellular energy in the form of adenosine triphosphate (ATP). Despite its high energy demands, the brain is relatively inflexible in its ability to utilize substrates for energy production and relies almost entirely on circulating glucose for its energy needs. This dependence on glucose puts the brain at risk if the supply of glucose is interrupted, or if its ability to metabolize glucose becomes defective. If the brain is not able to produce ATP, synapses cannot be maintained and cells cannot function, ultimately leading to impaired cognition.
Neurotoxicity
Glutamate is a chemical found in the brain that poses a toxic threat to neurons when found in high concentrations. This concentration equilibrium is extremely delicate and is usually found in millimolar amounts extracellularly. When disturbed, an accumulation of glutamate occurs as a result of a mutation in the glutamate transporters, which act like pumps to drain glutamate from the brain. This causes glutamate concentration to be several times higher in the blood than in the brain; in turn, the body must act to maintain equilibrium between the two concentrations by pumping the glutamate out of the bloodstream and into the neurons of the brain. In the event of a mutation, the glutamate transporters are unable to pump the glutamate back into the cells; thus a higher concentration accumulates at the glutamate receptors. This opens the ion channels, allowing calcium to enter the cell causing excitotoxicity. Glutamate results in cell death by turning on the N-methyl-D-aspartic acid receptors (NMDA); these receptors cause an increased release of calcium ions (Ca) into the cells. As a result, the increased concentration of Ca directly increases the stress on mitochondria, resulting in excessive oxidative phosphorylation and production of reactive oxygen species (ROS) via the activation of nitric oxide synthase, ultimately leading to cell death. Aβ was also found aiding this route to neurotoxicity by enhancing neuron vulnerability to glutamate.
Galanin
Galanin is located predominantly in the central nervous system and gastrointestinal tract. Within the central nervous system, highest concentrations are found in the hypothalamus, with lower levels in the cortex and brainstem. Gastrointestinal galanin is most abundant in the duodenum, with lower concentrations in the stomach, small intestine, and colon.
Drug delivery to the brain
The most promising drug delivery system is using nanoparticle delivery systems, these are systems where the drug is bound to a nanoparticle capable of traversing the blood–brain barrier. The most promising compound for the nanoparticles is Human Serum Albumin (HSA). The main benefits of this is that particles made of HSA are well tolerated without serious side effects as well as the albumin functional groups can be utilized for surface modification that allows for specific cell uptake. These nanoparticles have been shown to transverse the blood–brain barrier carrying host drugs. To enhance the effectiveness of nanoparticles, scientists are attempting to coat the nanoparticles to make them more effective to cross the blood–brain barrier. Studies have shown that "the overcoating of the [nanoparticles] with polysorbate 80 yielded doxorubicin concentrations in the brain of up to 6 μg/g after i.v. injection of 5 mg/kg" as compared to no detectable increase in an injection of the drug alone or the uncoated nanoparticle. This is very new science and technology so the real effectiveness of this process has not been fully understood. However young the research is the results are promising pointing to nanotechnology as the way forward in treating a variety of brain diseases.
5-HT1A receptor
The 5-HT receptor is the most widespread of all the 5-HT receptors. In the central nervous system, 5-HT receptors exist in the cerebral cortex, hippocampus, septum, amygdala, and raphe nucleus in high densities, while low amounts also exist in the basal ganglia and thalamus. The 5-HT receptors in the raphe nucleus are largely somatodendritic autoreceptors, whereas those in other areas such as the hippocampus are postsynaptic receptors.
Gliotransmitter
The word “glia” illustrates the original belief among scientists that these cells play a passive role in neural signaling, being responsible only for neuronal structure and support within the brain. Glial cells cannot produce action potentials and therefore were not suspected as playing an important and active communicative role in the central nervous system, because synaptic transmission between neurons is initiated with an action potential. However, research shows that these cells express excitability with changes in the intracellular concentrations of Ca. Gliotransmission occurs because of the ability of glial cells to induce excitability with variations in Ca concentrations. Changes in the concentration of Ca correlate with currents from NMDA receptor-mediated neurons which are measured in neighboring neurons of the ventrobasal (VB) thalamus. Because glial cells greatly outnumber neurons in the brain, accounting for over 70% of all cells in the central nervous system, gliotransmitters released by astrocytes have the potential to be very influential and important within the central nervous system, as well as within other neural systems throughout the body. These cells do not simply carry functions of structural support, but can also take part in cell-to-cell communication with neurons, microglia, and other astrocytes by receiving inputs, organizing information, and sending out chemical signals. The Ca signal from the astrocyte may also participate in controlling blood flow in the brain.
Addiction psychology
The neurochemical, glutamate is the most abundant neurochemical in the brain. It is critical in memory consolidation. When an addict discovers an addicting behavior, glutamate plays a role by creating the drug cues. It is the neurochemical in motivation which initiates the drug seeking, thus creating the addiction.
Brain
Axons transmit signals to other neurons by means of specialized junctions called synapses. A single axon may make as many as several thousand synaptic connections with other cells. When an action potential, traveling along an axon, arrives at a synapse, it causes a chemical called a neurotransmitter to be released. The neurotransmitter binds to receptor molecules in the membrane of the target cell.
Synapses are the key functional elements of the brain. The essential function of the brain is cell-to-cell communication, and synapses are the points at which communication occurs. The human brain has been estimated to contain approximately 100 trillion synapses; even the brain of a fruit fly contains several million. The functions of these synapses are very diverse: some are excitatory (exciting the target cell); others are inhibitory; others work by activating second messenger systems that change the internal chemistry of their target cells in complex ways. A large number of synapses are dynamically modifiable; that is, they are capable of changing strength in a way that is controlled by the patterns of signals that pass through them. It is widely believed that activity-dependent modification of synapses is the brain's primary mechanism for learning and memory.
Perineuronal net
PNNs appear to be mainly present in the cortex, hippocampus, thalamus, brainstem, and the spinal cord. Studies of the rat brain have shown that the cortex contains high numbers of PNNs in the motor and primary sensory areas and relatively fewer in the association and limbic cortices. In the cortex, PNNs are associated mostly with inhibitory interneurons and are thought to be responsible for maintaining the excitatory/inhibitory balance in the adult brain.
Neurokinin A
Neurokinin A (formally known as substance K) is a member of the tachykinin family of neuropeptide neurotransmitters. Tachykinins are important contributors to nociceptive processing, satiety, and smooth muscle contraction. Tachykinins are known to be highly excitatory neurotransmitters in major central neural systems. Neurokinin A is ubiquitous in both the central and peripheral mammalian nervous systems, and seems to be involved in reactions to pain and the inflammatory responses. It is produced from the same preprotachykinin A gene as the neuropeptide substance P. Both substance P and neurokinin A are encoded by the same mRNA, which when alternatively spliced can be translated into either compound. It has various roles in the body of humans and other animals, specifically stimulation of extravascular smooth muscle, vasodilation, hypertensive action, immune system activation, and pain management. The deduced amino acid sequence of neurokinin A is as follows: 
with amidation at the C-terminus.
Nicotine
By binding to nicotinic acetylcholine receptors in the brain, nicotine elicits its psychoactive effects and increases the levels of several neurotransmitters in various brain structures – acting as a sort of "volume control." Nicotine has a higher affinity for nicotinic receptors in the brain than those in skeletal muscle, though at toxic doses it can induce contractions and respiratory paralysis. Nicotine's selectivity is thought to be due to a particular amino acid difference on these receptor subtypes. Nicotine is unusual in comparison to most drugs, as its profile changes from stimulant to sedative with increasing dosages, a phenomenon known as "Nesbitt's paradox" after the doctor who first described it in 1969. At very high doses it dampens neuronal activity. Nicotine induces both behavioral stimulation and anxiety in animals. Research into nicotine's most predominant metabolite, cotinine, suggests that some of nicotine's psychoactive effects are mediated by cotinine.
Serotonin
The neurons of the raphe nuclei are the principal source of 5-HT release in the brain.
There are nine raphe nuclei, designated B1-B9, which contain the majority of serotonin-containing neurons (some scientists chose to group the "nuclei raphes lineares" into one nucleus), all of which are located along the midline of the brainstem, and centered on the reticular formation.
Axons from the neurons of the raphe nuclei form a neurotransmitter system reaching almost every part of the central nervous system. Axons of neurons in the lower raphe nuclei terminate in the cerebellum and spinal cord, while the axons of the higher nuclei spread out in the entire brain.
Tuberomammillary nucleus
The tuberomammillary nucleus is the sole source of histamine pathways in the human brain. The densest axonal projections from the tuberomammillary nucleus are sent to the cerebral cortex, hippocampus, neostriatum, nucleus accumbens, amygdala, and other parts of the hypothalamus. The projections to the cerebral cortex directly increase cortical activation and arousal, and projections to acetylcholinergic neurons of the basal forebrain and dorsal pons do so indirectly, by increasing the release of acetylcholine in the cerebral cortex.
Catecholamine
Catecholamines are produced mainly by the chromaffin cells of the adrenal medulla and the postganglionic fibers of the sympathetic nervous system. Dopamine, which acts as a neurotransmitter in the central nervous system, is largely produced in neuronal cell bodies in two areas of the brainstem: the ventral tegmental area and the substantia nigra, the latter of which contains neuromelanin-pigmented neurons. The similarly neuromelanin-pigmented cell bodies of the locus ceruleus produce norepinephrine. Epinephrine is produced in small groups of neurons in the human brain which express its synthesizing enzyme, phenylethanolamine "N"-methyltransferase; these neurons project from a nucleus that is adjacent (ventrolateral) to the area postrema and from a nucleus in the dorsal region of the solitary tract.
Neuropeptide
Neurons very often make both a conventional neurotransmitter (such as glutamate, GABA or dopamine) and one or more neuropeptides. Peptides are generally packaged in large dense-core vesicles, and the co-existing neurotransmitters in small synaptic vesicles. The large dense-core vesicles are often found in all parts of a neuron, including the soma, dendrites, axonal swellings (varicosities) and nerve endings, whereas the small synaptic vesicles are mainly found in clusters at presynaptic locations. Release of the large vesicles and the small vesicles is regulated differently.
Endocannabinoid system
Cannabinoid binding sites exist throughout the central and peripheral nervous systems. The two most relevant receptors for cannabinoids are the CB and CB receptors, which are expressed predominantly in the brain and immune system respectively. Density of expression varies based on species and correlates with the efficacy that cannabinoids will have in modulating specific aspects of behavior related to the site of expression. For example, in rodents, the highest concentration of cannabinoid binding sites are in the basal ganglia and cerebellum, regions of the brain involved in the initiation and coordination of movement. In humans, cannabinoid receptors exist in much lower concentration in these regions, which helps explain why cannabinoids possess a greater efficacy in altering rodent motor movements than they do in humans.
Neurotoxin
The nervous tissue found in the brain, spinal cord, and periphery comprises an extraordinarily complex biological system that largely defines many of the unique traits of individuals. As with any highly complex system, however, even small perturbations to its environment can lead to significant functional disruptions. Properties leading to the susceptibility of nervous tissue include a high surface area of neurons, a high lipid content which retains lipophilic toxins, high blood flow to the brain inducing increased effective toxin exposure, and the persistence of neurons through an individual's lifetime, leading to compounding of damages. As a result, the nervous system has a number of mechanisms designed to protect it from internal and external assaults, including the blood brain barrier.
Norepinephrine
The most important source of norepinephrine in the brain is the locus coeruleus, which contains noradrenergic cell group A6 and adjoins cell group A4. The locus coeruleus is quite small in absolute terms—in primates it is estimated to contain around 15,000 neurons, less than one millionth of the neurons in the brain—but it sends projections to every major part of the brain and also to the spinal cord.
Acetylcholine
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals, including humans, as a neurotransmitter—a chemical message released by nerve cells to send signals to other cells [neurons, muscle cells, and gland cells]. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Parts in the body that use or are affected by acetylcholine are referred to as cholinergic. Substances that interfere with acetylcholine activity are called anticholinergics.
Acetylcholine is the neurotransmitter used at the neuromuscular junction—in other words, it is the chemical that motor neurons of the nervous system release in order to activate muscles. This property means that drugs that affect cholinergic systems can have very dangerous effects ranging from paralysis to convulsions. Acetylcholine is also a neurotransmitter in the autonomic nervous system, both as an internal transmitter for the sympathetic nervous system and as the final product released by the parasympathetic nervous system.
Human brain
Below and in front of the striatum are a number of basal forebrain structures. These include the nucleus accumbens, nucleus basalis, diagonal band of Broca, substantia innominata, and the medial septal nucleus. These structures are important in producing the neurotransmitter, acetylcholine, which is then distributed widely throughout the brain. The basal forebrain, in particular the nucleus basalis, is considered to be the major cholinergic output of the central nervous system to the striatum and neocortex.
Norepinephrine
Norepinephrine is the main neurotransmitter used by the sympathetic nervous system, which consists of about two dozen sympathetic chain ganglia located next to the spinal cord, plus a set of prevertebral ganglia located in the chest and abdomen. These sympathetic ganglia are connected to numerous organs, including the eyes, salivary glands, heart, lungs, liver, gallbladder, stomach, intestines, kidneys, urinary bladder, reproductive organs, muscles, skin, and adrenal glands. Sympathetic activation of the adrenal glands causes the part called the adrenal medulla to release norepinephrine (as well as epinephrine) into the bloodstream, from which, functioning as a hormone, it gains further access to a wide variety of tissues.
N-Acetylaspartylglutamic acid
After its discovery in 1965, NAAG was disregarded as a neurotransmitter for several reasons. First, neuropeptides were not considered neurotransmitters until years later. Second, it did not seem to directly affect membrane potential, so it was classified as a metabolic intermediate. The importance of brain peptides became clearer with the discovery of endogenous opioids. Whereas the ability of NAAG to interact with NMDA receptors in a manner relevant to physiology is controversial, its primary receptor was long believed to be the mGluR3. Its interaction with the mGluR3 causes an activation of G proteins that reduce the concentration of the second messengers cAMP and cGMP in the both nerve cells and glia. This can lead to several changes in the cellular activity, including regulation of gene expression, reduction in the release of transmitter, and inhibition of long-term potentiation. Stimulation of the mGluR3 by NAAG has been, however, questioned, finding relevant glutamate contamination in commercially available NAAG.
Neurotoxin
Mercury is capable of inducing CNS damage by migrating into the brain by crossing the BBB. Mercury exists in a number of different compounds, though methylmercury (MeHg), dimethylmercury and diethylmercury are the only significantly neurotoxic forms. Diethylmercury and dimethylmercury are considered some of the most potent neurotoxins ever discovered. MeHg is usually acquired through consumption of seafood, as it tends to concentrate in organisms high on the food chain. It is known that the mercuric ion inhibits amino acid (AA) and glutamate (Glu) transport, potentially leading to excitotoxic effects.
Vitamin D and neurology
The brain requires the use of many neurosteroids to develop and function properly. These molecules are often identified as one of many common substances including thyroid hormones, glucocorticoids, and androgens. However in recent studies, throughout the brain and spinal fluid, vitamin D has begun to surface as one of these neurosteroids.The presence of vitamin D, its activating enzyme, and VDR in the brain leads researchers to question what role vitamin D plays in the brain. Research suggests that vitamin D may function as a modulator in brain development and as a neuroprotectant. In recent studies, vitamin D has exhibited an association with the regulation of nerve growth factor (NGF) synthesis. NGF is responsible for the growth and survival of neurons.
This relationship has also been studied in embryonic and neonatal rats. Developmental vitamin D deficient (DVD) rats have decreased levels of neurotrophic factors, increased mitosis, and decreased apoptosis. These findings suggest that vitamin D potentially affects the development of neurons as well as their maintenance and survival. Current research is underway investigating whether vitamin D is a factor contributing to normal brain functioning.
Neurotransmitter
Neurotransmitters are endogenous chemicals that enable neurotransmission. It is a type of chemical messenger which transmits signals across a chemical synapse, such as a neuromuscular junction, from one neuron (nerve cell) to another "target" neuron, muscle cell, or gland cell. Neurotransmitters are released from synaptic vesicles in synapses into the synaptic cleft, where they are received by neurotransmitter receptors on the target cells. Many neurotransmitters are synthesized from simple and plentiful precursors such as amino acids, which are readily available from the diet and only require a small number of biosynthetic steps for conversion. Neurotransmitters play a major role in shaping everyday life and functions. Their exact numbers are unknown, but more than 200 chemical messengers have been uniquely identified.
DUF1220
The copy number of DUF1220 domains increases generally as a function of a species's evolutionary proximity to humans. The increase in the number of copies that are present in connection with DUF1220 also seem to have a direct correlation with several phenotypes of the brain including the increase in brain size as seen through evolution. DUF1220 copy number is the highest in humans (~289, with some person-to-person variations) and shows the largest HLS increase in copy number (an additional 160 copies) of any protein coding region in the human genome. DUF1220 copy number is reduced in African great apes (estimated 125 copies in chimpanzees), further reduced in orangutan (92) and Old World monkeys (35), single- or low-copy in non-primate mammals and absent in non-mammals. DUF1220 domains are approximately 65 amino acids in length and are encoded by a two-exon doublet. In the human genome, DUF1220 sequences are located primarily on chromosome 1 in region 1q21.1-q21.2, with several copies also found at 1p36, 1p13.3, and 1p12. Sequences encoding DUF1220 domains show rhythmicity, resonance and signs of positive selection, especially in primates, and are expressed in several human tissues including brain, where their expression is restricted to neurons.
Neurotransmitter
Major neurotransmitters:In addition, over 50 neuroactive peptides have been found, and new ones are discovered regularly. Many of these are "co-released" along with a small-molecule transmitter. Nevertheless, in some cases a peptide is the primary transmitter at a synapse. β-endorphin is a relatively well-known example of a peptide neurotransmitter because it engages in highly specific interactions with opioid receptors in the central nervous system.
Brain-derived neurotrophic factor
One mechanism through which BDNF appears to maintain elevated levels of neuronal excitation is through preventing GABAergic signaling activities. While glutamate is the brain’s major excitatory neurotransmitter and phosphorylation normally activates receptors, GABA is the brain’s primary inhibitory neurotransmitter and phosphorylation of GABAA receptors tend to reduce their activity. Blockading BDNF signaling with a tyrosine kinase inhibitor or a PKC inhibitor in wild type mice produced significant reductions in spontaneous action potential frequencies that were mediated by an increase in the amplitude of GABAergic inhibitory postsynaptic currents (IPSC). Similar effects could be obtained in BDNF knockout mice, but these effects were reversed by local application of BDNF. 
This suggests BDNF increases excitatory synaptic signaling partly through the post-synaptic suppression of GABAergic signaling by activating PKC through its association with TrkB. Once activated, PKC can reduce the amplitude of IPSCs through to GABAA receptor phosphorylation and inhibition. In support of this putative mechanism, activation of PKCε leads to phosphorylation of N-ethylmaleimide-sensitive factor (NSF) at serine 460 and threonine 461, increasing its ATPase activity which downregulates GABAA receptor surface expression and subsequently attenuates inhibitory currents.
Relaxin-3
Relaxin-3 is mostly expressed within neurons of the brain, where it is packaged into dense cored vesicles and trafficked along axons where it can be detected in presynaptic vesicles before release onto target neurons, characteristic of a neurotransmitter. The largest number of relaxin-3-positive neurons in the rodent brain are within a region of the pontine brainstem known as the nucleus incertus, while smaller populations are present within the pontine raphe, periaqueductal grey, and an area dorsal to the substantia nigra. From these centres, relaxin-3 innervates a broad range of brain regions which are also rich in RXFP3 mRNA/binding sites, including the extended limbic system and the septohippocampal pathway.
Dehydroepiandrosterone
Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone. It is one of the most abundant circulating steroids in humans, in whom it is produced in the adrenal glands, the gonads, and the brain. It functions as a metabolic intermediate in the biosynthesis of the androgen and estrogen sex steroids both in the gonads and in various other tissues. However, DHEA also has a variety of potential biological effects in its own right, binding to an array of nuclear and cell surface receptors, and acting as a neurosteroid and modulator of neurotrophic factor receptors.
Enkephalin
Enkephalin is also considered a neuropeptide, which in the human body performs as an important signaling molecule in the brain. Enkephalins are found in high concentration in the brain as well as in the cells of adrenal medulla. In response to pain, norepinephrine, a hormone that is activated in fight-or-flight response is released along with endorphins. It has been shown that this polypeptide is linked to brain functioning during a stressful response, especially in the hippocampus and prefrontal cortex regions. During a stress response, several Met-enkephalin analogs had increased activity in the hippocampus, while Leu-enkephalin analogs as well as somatostatins were downregulated during stress. This observation leads to a conclusion that stressors impact neuropeptides, and that their action is localized to a specific brain region.
Brain
Neurotransmitters are chemicals that are released at synapses when an action potential activates them—neurotransmitters attach themselves to receptor molecules on the membrane of the synapse's target cell, and thereby alter the electrical or chemical properties of the receptor molecules.
With few exceptions, each neuron in the brain releases the same chemical neurotransmitter, or combination of neurotransmitters, at all the synaptic connections it makes with other neurons; this rule is known as Dale's principle. Thus, a neuron can be characterized by the neurotransmitters that it releases. The great majority of psychoactive drugs exert their effects by altering specific neurotransmitter systems. This applies to drugs such as cannabinoids, nicotine, heroin, cocaine, alcohol, fluoxetine, chlorpromazine, and many others.
Norepinephrine
In the brain, noradrenaline is produced in nuclei that are small yet exert powerful effects on other brain areas. The most important of these nuclei is the locus coeruleus, located in the pons. Outside the brain, norepinephrine is used as a neurotransmitter by sympathetic ganglia located near the spinal cord or in the abdomen, and it is also released directly into the bloodstream by the adrenal glands. Regardless of how and where it is released, norepinephrine acts on target cells by binding to and activating noradrenergic receptors located on the cell surface.
Chemoreceptor trigger zone
The CTZ is in the medulla oblongata, which is phylogenetically the oldest part of the nervous system. Early lifeforms developed a brainstem, or inner brain, and nothing more. This part of the brain is responsible for basic survival instincts and reactions, for example to make an organism turn its head and look where an auditory stimulus was heard. The brainstem is where the medulla is located, and therefore also the area postrema and the CTZ. Then later lifeforms developed another segment of the brain, which includes the limbic system. This area of the brain is responsible for producing emotion and emotional responses to external stimuli, and also is significantly involved in memory and reward systems. Evolutionarily, the cerebral cortex is the most recent development. This area of the brain is responsible for critical thinking and reasoning, and is actively involved in decision making. It has been discovered that a major cause of increased intelligence in species including humans is the increase in cortical neurons in the brain. The emetic response was selected for protective purposes, and serves as a safeguard against poisoning of the body. This response gets toxins and drugs out of the body by summoning control over motor neurons which stimulate muscles in the chest and thoracic diaphragm to expel contents from the stomach.
Neurobiological effects of physical exercise
Glutamate, one of the most common neurochemicals in the brain, is an excitatory neurotransmitter involved in many aspects of brain function, including learning and memory. Based upon animal models, exercise appears to normalize the excessive levels of glutamate neurotransmission into the nucleus accumbens that occurs in drug addiction. A review of the effects of exercise on neurocardiac function in preclinical models noted that exercise-induced neuroplasticity of the rostral ventrolateral medulla (RVLM) has an inhibitory effect on glutamatergic neurotransmission in this region, in turn reducing sympathetic activity; the review hypothesized that this neuroplasticity in the RVLM is a mechanism by which regular exercise prevents inactivity-related cardiovascular disease.
Neocortex
In the human brain, the neocortex is the largest part of the cerebral cortex which is the outer layer of the cerebrum, with the allocortex making up the rest. The neocortex is made up of six layers, labelled from the outermost inwards, I to VI. Of all the mammals studied to date (including humans), a species of oceanic dolphin known as the long-finned pilot whale has been found to have the most neocortical neurons.
Nervous system
According to a rule called Dale's principle, which has only a few known exceptions, a neuron releases the same neurotransmitters at all of its synapses. This does not mean, though, that a neuron exerts the same effect on all of its targets, because the effect of a synapse depends not on the neurotransmitter, but on the receptors that it activates. Because different targets can (and frequently do) use different types of receptors, it is possible for a neuron to have excitatory effects on one set of target cells, inhibitory effects on others, and complex modulatory effects on others still. Nevertheless, it happens that the two most widely used neurotransmitters, glutamate and GABA, each have largely consistent effects. Glutamate has several widely occurring types of receptors, but all of them are excitatory or modulatory. Similarly, GABA has several widely occurring receptor types, but all of them are inhibitory. Because of this consistency, glutamatergic cells are frequently referred to as "excitatory neurons", and GABAergic cells as "inhibitory neurons". Strictly speaking, this is an abuse of terminology—it is the receptors that are excitatory and inhibitory, not the neurons—but it is commonly seen even in scholarly publications.
Neuroligin
Expression of neuroligins may differ between species. Neuroligin 1 is expressed specifically in the CNS at excitatory synapses. In humans, expression of neuroligin 1 is low before birth and increases between postnatal days 1-8 and remains high through adulthood. This postnatal increase during active synaptogenesis corresponds to increased expression of postsynaptic density protein-95 (PSD-95). Neuroligin 2 is mainly concentrated at inhibitory synapses in the CNS, but in mice and humans it may also be expressed in tissues such as the pancreas, lung, endothelia, uterus and colon. Neuroligin 3 is expressed in CNS neurons, as well as a variety of glial cells in mice and rats and the brain, heart, skeletal muscle, placenta and pancreas in humans. Neuroligin 4X, found only in humans, is expressed in the heart, liver, skeletal muscle, pancreas and low levels in the brain. Neuroligin 5 (or 4Y), located on the Y chromosome, is only 19 amino acids different from neuroligin 4X. Neuroligin mRNA are present in human endothelial cells from large blood vessels and in Dorsal Root Ganglions.
Neural oscillation
In addition to fast direct synaptic interactions between neurons forming a network, oscillatory activity is regulated by neuromodulators on a much slower time scale. That is, the concentration levels of certain neurotransmitters are known to regulate the amount of oscillatory activity. For instance, GABA concentration has been shown to be positively correlated with frequency of oscillations in induced stimuli. A number of nuclei in the brainstem have diffuse projections throughout the brain influencing concentration levels of neurotransmitters such as norepinephrine, acetylcholine and serotonin. These neurotransmitter systems affect the physiological state, e.g., wakefulness or arousal, and have a pronounced effect on amplitude of different brain waves, such as alpha activity.
Behavioral epigenetics
Epigenetic changes including hypomethylation of glutamatergic genes (i.e., NMDA-receptor-subunit gene NR3B and the promoter of the AMPA-receptor-subunit gene GRIA2) in the post-mortem human brains of schizophrenics are associated with increased levels of the neurotransmitter glutamate. Since glutamate is the most prevalent, fast, excitatory neurotransmitter, increased levels may result in the psychotic episodes related to schizophrenia. Epigenetic changes affecting a greater number of genes have been detected in men with schizophrenia as compared to women with the illness.
Hippocampus
Because of its densely packed neural layers, of all the brain structures which generate the "hippocampal theta rhythm", the hippocampus generates some of the largest EEG signals as theta waves . In some situations the EEG is dominated by regular waves at 3 to 10 Hz, often continuing for many seconds. These reflect subthreshold membrane potentials and strongly modulate the spiking of hippocampal neurons and synchronise across the hippocampus in a travelling wave pattern. The trisynaptic circuit is a relay of neurotransmission in the hippocampus that interacts with many brain regions. From rodent studies it has been proposed that the trisynaptic circuit generates the hippocampal theta rhythm.
List of animals by number of neurons
The whole human brain contains 86 billion neurons and roughly 16 billion neurons in the cerebral cortex.
Orexin-A
Orexins are highly excitatory neuropeptides that were first discovered in the brains of rats. It is a peptide that is produced by a very small population of cells in the lateral and posterior hypothalamus. Orexins strongly excite various brain nuclei (neurons) to affect an organism’s wakefulness by affecting their dopamine, norepinephrine, histamine and acetylcholine systems. These systems work together to stabilize the organism’s sleep cycles. Once made, the orexin peptides can bind to the orexin receptor; which is a G protein coupled receptor. This G protein linked receptor senses molecules outside the cell and activates inside signal transduction pathways to elicit cellular responses.
Arvid Carlsson
In 1957 Kathleen Montagu demonstrated the presence of dopamine in the human brain; later that same year Carlsson also demonstrated that dopamine was a neurotransmitter in the brain and not just a precursor for norepinephrine. Carlsson went on to develop a method for measuring the amount of dopamine in brain tissues. He found that dopamine levels in the basal ganglia, a brain area important for movement, were particularly high. He then showed that giving animals the drug reserpine caused a decrease in dopamine levels and a loss of movement control. These effects were similar to the symptoms of Parkinson's disease. By administering to these animals L-Dopa, which is the precursor of dopamine, he could alleviate the symptoms. These findings led other doctors to try using L-Dopa in patients with Parkinson's disease, and it was found to alleviate some of the symptoms in the early stages of the disease. L-Dopa is still the basis for most commonly used means of treating Parkinson's disease.
Gitte Moos Knudsen
Knudsen is one of the leading figures in the neurosciences, assisting various European Union nations to prioritize research and grants. In addition, her research into the brain and its chemistry during depression, Alzheimer's Disease, and states induced by drugs such as GHB and ecstasy (MDMA) is at the forefront of world knowledge, and she is a noted scholar in these areas, publishing many papers on each topic. Her interest in brain imaging has led to a deeper understanding of how many receptors act within the brain, and she has produced studies using SPECT, PET, and MRI results to interpret these. A key issue is that the latest brain research not only contributes to increased understanding of brain functions, but is also used to attempt to explain what it means to be human.
Neuron
The human brain has a huge number of synapses. Each of the 10 (one hundred billion) neurons has on average 7,000 synaptic connections to other neurons. It has been estimated that the brain of a three-year-old child has about 10 synapses (1 quadrillion). This number declines with age, stabilizing by adulthood. Estimates vary for an adult, ranging from 10 to 5 x 10 synapses (100 to 500 trillion).
In 1937, John Zachary Young suggested that the squid giant axon could be used to study neuronal electrical properties. Being larger than but similar in nature to human neurons, squid cells were easier to study. By inserting electrodes into the giant squid axons, accurate measurements were made of the membrane potential.
Neurotoxin
Though nitric oxide (NO) is commonly used by the nervous system in inter-neuron communication and signaling, it can be active in mechanisms leading to ischemia in the cerebrum (Iadecola 1998). The neurotoxicity of NO is based on its importance in glutamate excitotoxicity, as NO is generated in a calcium-dependent manner in response to glutamate mediated NMDA activation, which occurs at an elevated rate in glutamate excitotoxicity. Though NO facilitates increased blood flow to potentially ischemic regions of the brain, it is also capable of increasing oxidative stress, inducing DNA damage and apoptosis. Thus an increased presence of NO in an ischemic area of the CNS can produce significantly toxic effects.
Protriptyline
Protriptyline acts by decreasing the reuptake of norepinephrine and to a lesser extent serotonin (5-HT) in the brain. Its affinity for the human norepinephrine transporter (NET) is 1.41 nM, 19.6 nM for the serotonin transporter and 2,100 nM for the dopamine transporter. TCAs act to change the balance of naturally occurring chemicals in the brain that regulate the transmission of nerve impulses between cells. Protriptyline increases the concentration of norepinephrine and serotonin (both chemicals that stimulate nerve cells) and, to a lesser extent, blocks the action of another brain chemical, acetylcholine. The therapeutic effects of protriptyline, like other antidepressants, appear slowly. Maximum benefit is often not evident for at least two weeks after starting the drug.
Neurotransmitter
Most neurotransmitters are about the size of a single amino acid, however, some neurotransmitters may be the size of larger proteins or peptides. A released neurotransmitter is typically available in the synaptic cleft for a short time before it is metabolized by enzymes, pulled back into the presynaptic neuron through reuptake, or bound to a postsynaptic receptor. Nevertheless, short-term exposure of the receptor to a neurotransmitter is typically sufficient for causing a postsynaptic response by way of synaptic transmission.
Betaine transporter
The mammalian betaine transporter (BGT1; SLC6A12 is predominantly expressed in the liver (hepatocytes). It is also expressed in the kidney where it is regulated by NFAT5 during a response to osmotic stress. Further, BGT1 is also present in the leptomeninges surrounding the brain. Deletion of the BGT1 gene in mice did not appear to have any impact on the tendency to develop epilepsy. This is to be expected considering that BGT1 is expressed at far lower levels than GAT1 and also has lower affinity for GABA. This implies that it is not likely to contribute significantly to the inactivation of the inhibitory neurotransmitter GABA.
GABRG2
Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain, mediates neuronal inhibition by binding to GABA receptors. The type A GABA receptors are pentameric chloride channels assembled from among many genetic variants of GABA(A) subunits. This gene encodes the gamma 2 subunit of GABA(A) receptor. Mutations in this gene have been associated with epilepsy and febrile seizures. Alternative splicing of this gene results in transcript variants encoding different isoforms.
Brain
There are dozens of other chemical neurotransmitters that are used in more limited areas of the brain, often areas dedicated to a particular function. Serotonin, for example—the primary target of antidepressant drugs and many dietary aids—comes exclusively from a small brainstem area called the raphe nuclei. Norepinephrine, which is involved in arousal, comes exclusively from a nearby small area called the locus coeruleus. Other neurotransmitters such as acetylcholine and dopamine have multiple sources in the brain, but are not as ubiquitously distributed as glutamate and GABA.
Benzodiazepine withdrawal syndrome
It has been postulated that when benzodiazepines are cleared from the brain, these neuroadaptations are "unmasked", leading to unopposed excitability of the neuron.
Glutamate is the most abundant excitatory neurotransmitter in the vertebrate nervous system. Increased glutamate excitatory activity during withdrawal may lead to sensitization or kindling of the CNS, possibly leading to worsening cognition and symptomatology and making each subsequent withdrawal period worse. Those who have a prior history of withdrawing from benzodiazepines are found to be less likely to succeed the next time around.
Neuromedin U
Neuromedin U (or NmU) is a neuropeptide found in the brain of humans and other mammals, which has a number of diverse functions including contraction of smooth muscle, regulation of blood pressure, pain perception, appetite, bone growth, and hormone release. It was first isolated from the spinal cord in 1985, and named after its ability to cause smooth muscle contraction in the uterus.
Ketogenic diet
The brain is composed of a network of neurons that transmit signals by propagating nerve impulses. The propagation of this impulse from one neuron to another is typically controlled by neurotransmitters, though there are also electrical pathways between some neurons. Neurotransmitters can inhibit impulse firing (primarily done by γ-aminobutyric acid, or GABA) or they can excite the neuron into firing (primarily done by glutamate). A neuron that releases inhibitory neurotransmitters from its terminals is called an inhibitory neuron, while one that releases excitatory neurotransmitters is an excitatory neuron. When the normal balance between inhibition and excitation is significantly disrupted in all or part of the brain, a seizure can occur. The GABA system is an important target for anticonvulsant drugs, since seizures may be discouraged by increasing GABA synthesis, decreasing its breakdown, or enhancing its effect on neurons.
2-Arachidonoylglycerol
2-AG, unlike anandamide (another endocannabinoid), is present at relatively high levels in the central nervous system; it is the most abundant molecular species of monoacylglycerol found in mouse and rat brain (~5-10 nmol/g tissue). Detection of 2-AG in brain tissue is complicated by the relative ease of its isomerization to 1-AG during standard lipid extraction conditions. It has been found in maternal bovine as well as human milk.
Sialic acid
It has been demonstrated that the human brain has more sialic acid than the brains of other mammals (2 – 4 times more). Neural membranes have 20 times more sialic acid than other cellular membranes. It is believed that sialic acid has a decisive role in enabling neurotransmission between neurons. The effects of sialic acid supplementation on learning and memory behaviour has been studied in rodents, as well as in piglets (whose brain structure and function more closely resemble those of humans). A diet rich in sialic acid was given to newborn piglets for five weeks. Then learning and memory were evaluated using a visual cue in a maze. A relationship between dietary sialic acid supplementation and cognitive function was seen: the piglets that had been fed high doses of sialic acid learned more quickly and made fewer mistakes. This suggests that sialic acid has an influence upon brain development and learning.
N-Acetylaspartic acid
However, the recent discovery of a higher concentration of NAA in myelin and oligodendrocytes than in neurons raises questions about the validity of the use of NAA as a neuronal marker. NAA gives off the largest signal in magnetic resonance spectroscopy of the human brain. The levels measured there are decreased in numerous neuropathological conditions ranging from brain injury to stroke to Alzheimer's disease. This fact makes NAA a potential diagnostic molecule for doctors treating patients with brain damage or disease.
Solomon H. Snyder
Solomon Halbert Snyder (born December 26, 1938) is an American neuroscientist who is known for wide-ranging contributions to neuropharmacology and neurochemistry. He studied at Georgetown University, and has conducted the majority of his research at the Johns Hopkins School of Medicine. Many advances in molecular neuroscience have stemmed from Dr. Snyder's identification of receptors for neurotransmitters and drugs, and elucidation of the actions of psychotropic agents, making him one of the most highly cited biologists in the world. He is most famous for his research on the opioid receptor, for which he received the Albert Lasker Award for Basic Medical Research in 1978. As of October 2018, Snyder is the most cited researcher (by h-index), according to Google Scholar Citations public profiles.
Nucleus basalis
The nucleus basalis, also known as the nucleus basalis of Meynert or nucleus basalis magnocellularis, is a group of neurons located mainly in the substantia innominata of the basal forebrain. Most neurons of the nucleus basalis are rich in the neurotransmitter acetylcholine, and they have widespread projections to the neocortex and other brain structures.
Dizocilpine
Dizocilpine (INN), also known as MK-801, is a noncompetitive antagonist of the "N"-Methyl--aspartate (NMDA) receptor, a glutamate receptor, discovered by a team at Merck in 1982. Glutamate is the brain's primary excitatory neurotransmitter. The channel is normally blocked with a magnesium ion and requires depolarization of the neuron to remove the magnesium and allow the glutamate to open the channel, causing an influx of calcium, which then leads to subsequent depolarization. Dizocilpine binds inside the ion channel of the receptor at several of PCP's binding sites thus preventing the flow of ions, including calcium (Ca), through the channel. Dizocilpine blocks NMDA receptors in a use- and voltage-dependent manner, since the channel must open for the drug to bind inside it. The drug acts as a potent anti-convulsant and likely has dissociative anesthetic properties, but it is not used clinically for this purpose due to the discovery of brain lesions, called Olney's lesions (see below), in lab rats. Dizocilpine is also associated with a number of negative side effects, including cognitive disruption and psychotic-spectrum reactions. It also inhibited the induction of long term potentiation. Instead, the NMDA receptor pore-blocker ketamine is used as a dissociative anesthetic in human medical procedures. While ketamine may also trigger temporary psychosis in certain individuals, its short half-life and lower potency make it a much safer clinical option. However, dizocilpine is the most frequently used non-competitive NMDA receptor antagonist in animal models to mimic psychosis for experimental purposes.
Nicotine dependence
Pre-existing cognitive and mood disorders may influence the development and maintenance of nicotine dependence. Nicotine is a parasympathomimetic stimulant that binds to and activates nicotinic acetylcholine receptors in the brain, which subsequently causes the release of dopamine and other neurotransmitters, such as norepinephrine, acetylcholine, serotonin, gamma-aminobutyric acid, glutamate, endorphins, and several neuropeptides. Repeated exposure to nicotine can cause an increase in the number of nicotinic receptors, which is believed to be a result of receptor desensitization and subsequent receptor upregulation. This upregulation or increase in the number of nicotinic receptors significantly alters the functioning of the brain reward system. With constant use of nicotine, tolerance occurs at least partially as a result of the development of new nicotinic acetylcholine receptors in the brain. After several months of nicotine abstinence, the number of receptors go back to normal. Nicotine also stimulates nicotinic acetylcholine receptors in the adrenal medulla, resulting in increased levels of adrenaline and beta-endorphin. Its physiological effects stem from the stimulation of nicotinic acetylcholine receptors, which are located throughout the central and peripheral nervous systems. Chronic nicotinic acetylcholine receptor activation from repeated nicotine exposure can induce strong effects on the brain, including changes in the brain's physiology, that result from the stimulation of regions of the brain associated with reward, pleasure, and anxiety. These complex effects of nicotine on the brain are still not well understood.
Amphetamine
In addition to the neuronal monoamine transporters, amphetamine also inhibits both vesicular monoamine transporters, VMAT1 and VMAT2, as well as SLC1A1, SLC22A3, and SLC22A5. SLC1A1 is excitatory amino acid transporter 3 (EAAT3), a glutamate transporter located in neurons, SLC22A3 is an extraneuronal monoamine transporter that is present in astrocytes, and SLC22A5 is a high-affinity carnitine transporter. Amphetamine is known to strongly induce cocaine- and amphetamine-regulated transcript (CART) gene expression, a neuropeptide involved in feeding behavior, stress, and reward, which induces observable increases in neuronal development and survival "in vitro". The CART receptor has yet to be identified, but there is significant evidence that CART binds to a unique . Amphetamine also inhibits monoamine oxidases at very high doses, resulting in less monoamine and trace amine metabolism and consequently higher concentrations of synaptic monoamines. In humans, the only post-synaptic receptor at which amphetamine is known to bind is the receptor, where it acts as an agonist with micromolar affinity.
Neurotransmitter
Until the early 20th century, scientists assumed that the majority of synaptic communication in the brain was electrical. However, through the careful histological examinations by Ramón y Cajal (1852–1934), a 20 to 40 nm gap between neurons, known today as the synaptic cleft, was discovered. The presence of such a gap suggested communication via chemical messengers traversing the synaptic cleft, and in 1921 German pharmacologist Otto Loewi (1873–1961) confirmed that neurons can communicate by releasing chemicals. Through a series of experiments involving the vagus nerves of frogs, Loewi was able to manually slow the heart rate of frogs by controlling the amount of saline solution present around the vagus nerve. Upon completion of this experiment, Loewi asserted that sympathetic regulation of cardiac function can be mediated through changes in chemical concentrations. Furthermore, Otto Loewi is credited with discovering acetylcholine (ACh)—the first known neurotransmitter. Some neurons do, however, communicate via electrical synapses through the use of gap junctions, which allow specific ions to pass directly from one cell to another.
Spinal interneuron
The sensory information that is transmitted to the spinal cord is modulated by a complex network of excitatory and ihibitory interneurons. Different neurotransmitters are released from different interneurons, but the two most common neurotransmitters are GABA, the primary inhibitory neurotransmitter and glutamate, the primary excitatory neurotransmitter. Acetylcholine is a neurotransmitter that often activates interneurons by binding to a receptor on the membrane.
Neuromedin U
Neuromedin U is a highly conserved neuropeptide present in many species, existing as multiple isoforms. For example, in humans it is a 25 amino acid peptide (U-25) in rats it is 23-aas long (U-23) and it has been found to be as low as 8-aas long in some mammals. NMU-8 is identical to the C terminus of NMU-25, thus is the most highly conserved region of the entire peptide. The relative contribution of the different isoforms to the biological function of neuromedin U is generally not well understood. Neuromedin U, like many neuroactive peptides, is amidated at the C-terminus, and all isoforms have identical C-terminal heptapeptides.
Dorsal nexus
Since glutamate is the most abundant and major excitatory neurotransmitter in the brain, pathophysiological changes in glutamatergic signaling are likely to affect neurobehavioral plasticity, information processing and large-scales changes in functional brain connectivity.Ketamine, a fast-acting general anesthetic derived from phencyclidine and use as a pediatric inductor, plays a non-well known role in the neural network dynamics at the healthy brain . The administration of ketamine in abnormal brain has the potential of reduce the increased function of the networks that are seen in depression. The therapeutic potential of ketamine may be explained by reversing disturbances in the glutamatergic system and restoring parts of a disrupted neurobehavioral homeostasis where several structural, metabolic, and functional abnormalities have taken place. Long term ketamine treatments lead to cognitive impairment including problems of short-term memory, visual and verbal memory. On the other hand, short term treatments are generally well tolerated and any damage may be reversible.
Neurotransmitter
The most prevalent transmitter is glutamate, which is excitatory at well over 90% of the synapses in the human brain. The next most prevalent is Gamma-Aminobutyric Acid, or GABA, which is inhibitory at more than 90% of the synapses that do not use glutamate. Although other transmitters are used in fewer synapses, they may be very important functionally: the great majority of psychoactive drugs exert their effects by altering the actions of some neurotransmitter systems, often acting through transmitters other than glutamate or GABA. Addictive drugs such as cocaine and amphetamines exert their effects primarily on the dopamine system. The addictive opiate drugs exert their effects primarily as functional analogs of opioid peptides, which, in turn, regulate dopamine levels.
Neuropil
Neuropil (or "neuropile") is any area in the nervous system composed of mostly unmyelinated axons, dendrites and glial cell processes that forms a synaptically dense region containing a relatively low number of cell bodies. The most prevalent anatomical region of neuropil is the brain which, although not completely composed of neuropil, does have the largest and highest synaptically-concentrated areas of neuropil in the body. For example, the neocortex and olfactory bulb both contain neuropil.
Cerebellum
Cerebellar granule cells, in contrast to Purkinje cells, are among the smallest neurons in the brain. They are also easily the most numerous neurons in the brain: In humans, estimates of their total number average around 50 billion, which means that about 3/4 of the brain's neurons are cerebellar granule cells. Their cell bodies are packed into a thick layer at the bottom of the cerebellar cortex. A granule cell emits only four to five dendrites, each of which ends in an enlargement called a "dendritic claw". These enlargements are sites of excitatory input from mossy fibers and inhibitory input from Golgi cells.
Norepinephrine transporter
Norepinephrine (NE) is released from noradrenergic neurons that innervate both the CNS and PNS. NE, also known as noradrenaline (NA), has an important role in controlling mood, arousal, memory, learning, and pain perception. NE is a part of the sympathetic nervous system. Dysregulation of the removal of norepinephrine by NET is associated with many neuropsychiatric diseases, discussed below. In addition, many antidepressants and recreational drugs compete for the binding of NET with NE.
Dopamine
Dopaminergic neurons (dopamine-producing nerve cells) are comparatively few in number—a total of around 400,000 in the human brain—and their cell bodies are confined in groups to a few relatively small brain areas. However their axons project to many other brain areas, and they exert powerful effects on their targets. These dopaminergic cell groups were first mapped in 1964 by Annica Dahlström and Kjell Fuxe, who assigned them labels starting with the letter "A" (for "aminergic"). In their scheme, areas A1 through A7 contain the neurotransmitter norepinephrine, whereas A8 through A14 contain dopamine. The dopaminergic areas they identified are the substantia nigra (groups 8 and 9); the ventral tegmental area (group 10); the posterior hypothalamus (group 11); the arcuate nucleus (group 12); the zona incerta (group 13) and the periventricular nucleus (group 14).
Inositol
Inositol, or more precisely "myo"-inositol, is a carbocyclic sugar that is abundant in brain and other mammalian tissues, mediates cell signal transduction in response to a variety of hormones, neurotransmitters and growth factors and participates in osmoregulation. It is a sugar alcohol with half the sweetness of sucrose (table sugar). It is made naturally in humans from glucose. Each kidney makes 2g a day; so 4g a day total is made. Other tissues synthesize it too, and the highest concentration is in the brain where it plays an important role making other neurotransmitters, and some steroid hormones bind to their receptors.
Orexin
There are only 10,000–20,000 orexin-producing neurons in the human brain, located predominantly in the perifornical area and lateral hypothalamus. They project widely throughout the central nervous system, regulating wakefulness, feeding, and other behaviours. There are two types of orexin peptide and two types of orexin receptor.
Cerebellar granule cell
Cerebellar granule cells form the thick granular layer of the cerebellar cortex and are among the smallest neurons in the brain. (The term granule cell is used for several unrelated types of small neurons in various parts of the brain.) Cerebellar granule cells are also the most numerous neurons in the brain: in humans, estimates of their total number average around 50 billion, which means that they constitute about 3/4 of the brain's neurons.
Supraoptic nucleus
Of the afferent inputs to the supraoptic nucleus, most contain either the inhibitory neurotransmitter GABA or the excitatory neurotransmitter glutamate, but these transmitters often co-exist with various peptides. Other afferent neurotransmitters include noradrenaline (from the brainstem), dopamine, serotonin, and acetylcholine.
Neuroeconomics
The neurotransmitter serotonin seems to play an important role in modulating future discounting. In rats, reducing serotonin levels increases future discounting while not affecting decision making under uncertainty. It seems, then, that while the dopamine system is involved in probabilistic uncertainty, serotonin may be responsible for temporal uncertainty since delayed reward involves a potentially uncertain future. In addition to neurotransmitters, intertemporal choice is also modulated by hormones in the brain. In humans, a reduction in cortisol, released by the hypothalamus in response to stress, is correlated with a higher degree of impulsivity in intertemporal choice tasks. Drug addicts tend to have lower levels of cortisol than the general population, which may explain why they seem to discount the future negative effects of taking drugs and opt for the immediate positive reward.
Interneuron
Unlike the peripheral nervous system (PNS), the central nervous system, including the brain, contains many interneurons. In the neocortex (making up about 80% of the human brain), approximately 20-30% of neurons are interneurons. Investigations into the molecular diversity of neurons is impeded by the inability to isolate cell populations born at different times for gene expression analysis. An effective means of identifying coetaneous interneurons is neuronal birthdating. This can be achieved using nucleoside analogs such as EdU.
Glia
In general, neuroglial cells are smaller than neurons. There are approximately 85 billion glia cells in the human brain, about the same number as neurons. Glial cells make up about half the total volume of the brain and spinal cord. The glia to neuron-ratio varies from one part of the brain to another. The glia to neuron-ratio in the cerebral cortex is 3.72 (60.84 billion glia (72%); 16.34 billion neurons), while that of the cerebellum is only 0.23 (16.04 billion glia; 69.03 billion neurons). The ratio in the cerebral cortex gray matter is 1.48, with 3.76 for the gray and white matter combined. The ratio of the basal ganglia, diencephalon and brainstem combined is 11.35.
Neuroscience of rhythm
The neuroscience of rhythm refers to the various forms of rhythm generated by the central nervous system (CNS). Nerve cells, also known as neurons in the human brain are capable of firing in specific patterns which cause oscillations. The brain possesses many different types of oscillators with different periods. Oscillators are simultaneously outputting frequencies from .02 Hz to 600 Hz. It is now well known that a computer is capable of running thousands of processes with just one high frequency clock. Humans have many different clocks as a result of evolution. Prior organisms had no need for a fast responding oscillator. This multi-clock system permits quick response to constantly changing sensory input while still maintaining the autonomic processes that sustain life. This method modulates and controls a great deal of bodily functions.
Nicotinic agonist
In the human nervous system nicotinic cholinergic signals are extended throughout the system, where the neurotransmitter acetylcholine (ACh) plays a key role in activating ligand-gated ion channels. The cholinergic system is a vital nervous pathway, where cholinergic neurons synthesize, store and release the neurotransmitter ACh. The main receptors that convert the ACh messages are the cholinergic muscarinic acetylcholine receptors, neuronal and muscular nAChRs. When looking back at evolutionary history, ACh is considered to be the oldest transmitter molecule and became present before the nervous cell. In the nervous system cholinergic stimulation mediated through nAChRs controls pathways such as release of transmitters and cell sensitivity, which can influence physiological activity including sleep, anxiety, processing of pain and cognitive functions.
Reward system
Addictive drugs and behaviors are rewarding and reinforcing (i.e., are "addictive") due to their effects on the dopamine reward pathway.
The lateral hypothalamus and medial forebrain bundle has been the most-frequently-studied brain-stimulation reward site, particularly in studies of the effects of drugs on brain stimulation reward. The neurotransmitter system that has been most-clearly identified with the habit-forming actions of drugs-of-abuse is the mesolimbic dopamine system, with its efferent targets in the nucleus accumbens and its local GABAergic afferents. The reward-relevant actions of amphetamine and cocaine are in the dopaminergic synapses of the nucleus accumbens and perhaps the medial prefrontal cortex. Rats also learn to lever-press for cocaine injections into the medial prefrontal cortex, which works by increasing dopamine turnover in the nucleus accumbens. Nicotine infused directly into the nucleus accumbens also enhances local dopamine release, presumably by a presynaptic action on the dopaminergic terminals of this region. Nicotinic receptors localize to dopaminergic cell bodies and local nicotine injections increase dopaminergic cell firing that is critical for nicotinic reward. Some additional habit-forming drugs are also likely to decrease the output of medium spiny neurons as a consequence, despite activating dopaminergic projections. For opiates, the lowest-threshold site for reward effects involves actions on GABAergic neurons in the ventral tegmental area, a secondary site of opiate-rewarding actions on medium spiny output neurons of the nucleus accumbens. Thus GABAergic afferents to the mesolimbic dopamine neurons (primary substrate of opiate reward), the mesolimbic dopamine neurons themselves (primary substrate of psychomotor stimulant reward), and GABAergic efferents to the mesolimbic dopamine neurons (a secondary site of opiate reward) form the core of currently characterized drug-reward circuitry.
Sandra Witelson
Sandra Freedman Witelson is a Canadian neuroscientist best known for her analysis of specimens from Albert Einstein's brain, as well as exploring anatomic and functional differences regarding male and female brains, handedness, and sexual orientation. She and her colleagues maintain the world's largest collection of "cognitively normal" brains (numbering 125 as of 2006) at McMaster University in Hamilton, Ontario.
GABA transporter
GABA transporter group consists of six different transporters:GAT1 and GAT3 are the major GABA transporters in the brain and spinal cord, expressed by both neurons and some astrocytes. GAT2 and BGT1 are also expressed in the brain, but at low levels and mostly in the meninges. GAT2 also transports taurine, while BGT1 transports betaine. These two transporters are predominantly expressed in the liver, but are also found in the kidneys and, as mentioned above, in the meninges.
Spindle neuron
The largest number of ACC spindle neurons are found in humans, fewer in the gracile great apes, and fewest in the robust great apes. In both humans and bonobos they are often found in clusters of 3 to 6 neurons. They are found in humans, bonobos, common chimpanzees, gorillas, orangutans, some cetaceans, and elephants. While total quantities of ACC spindle neurons were not reported by Allman in his seminal research report (as they were in a later report describing their presence in the frontoinsular cortex, below), his team's initial analysis of the ACC layer V in hominids revealed an average of ~9 spindle neurons per section for orangutans (rare, 0.6% of section cells), ~22 for gorillas (frequent, 2.3%), ~37 for chimpanzees (abundant, 3.8%), ~68 for bonobos (abundant/clusters, 4.8%), ~89 for humans (abundant/clusters, 5.6%).
Brain
The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. The brain is located in the head, usually close to the sensory organs for senses such as vision. The brain is the most complex organ in a vertebrate's body. In a human, the cerebral cortex contains approximately 14–16 billion neurons, and the estimated number of neurons in the cerebellum is 55–70 billion. Each neuron is connected by synapses to several thousand other neurons. These neurons communicate with one another by means of long protoplasmic fibers called axons, which carry trains of signal pulses called action potentials to distant parts of the brain or body targeting specific recipient cells.
N-Acetylaspartic acid
NAA is the second-most-concentrated molecule in the brain after the amino acid glutamate. It is detected in the adult brain in neurons, oligodendrocytes and myelin and is synthesized in the mitochondria from the amino acid aspartic acid and acetyl-coenzyme A.
Nidopallium
The entire nidopallium region is a compelling area for neuroscientific research, especially in relation to its capacity for complex cognitive function. More specifically, the nidopallium caudolateral appears particularly involved with the aspect of executive function in the avian brain. One study has been performed to demonstrate that this area is in fact largely analogous to the mammalian prefrontal cortex - the region of the brain covering the most rostral section of the frontal lobe, responsible for more complex cognitive behaviour in mammals, such as ourselves. The experiment sought to measure the densities of various neurotransmitter receptors in both the avian NCL and the human prefrontal cortex, using quantitative in-vitro receptor autoradiography. It was found that the NCL contained lower absolute quantities of these neuronal receptors. However, the experiment also revealed that the relative densities of these receptors in both organisms were surprisingly similar. With this, there is the possible implication that the capability for such sophisticated mental processes in these structures is reliant on the receptor architecture of the neurons which comprise them. So despite the nidopallium and prefrontal cortex having evolved separately (an educated assumption), both have achieved similar functions of higher order thought processes via convergent evolution, as a result of influences at the molecular level.
Neuromodulation
Neurotransmitter systems are systems of neurons in the brain expressing certain types of neurotransmitters, and thus form distinct systems. Activation of the system causes effects in large volumes of the brain, called "volume transmission". Volume transmission is the diffusion of neurotransmitters through the brain extracellular fluid released at points that may be remote from the target cells with the resulting activation of extrasynaptic receptors, and with a longer time course than for transmission at a single synapse. Such prolonged transmitter action is called tonic transmission, in contrast to the phasic transmission that occurs rapidly at single synapses.
Choline transporter
Choline is a necessary reagent for the synthesis of acetylcholine in the central nervous system. Neurons get their choline by specific protein transporters known as choline transporters. In the human brain microvascular endothelial cells, two systems initiate the choline absorption. The first system is known as the Choline transporter-like protein 1, or CTL1. The second system is the Choline transporter-like protein 2, or CTL2. Those two systems are found on the plasma membrane of the brain microvascular endothelial cells. They are also found on the mitochondrial membrane. CTL2 was found to be highly expressed on the mitochondria. Meanwhile, CTL1 was mostly found on the plasma membrane of those microvascular cells.
Neurotrophin
Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor found originally in the brain, but also found in the periphery. To be specific, it is a protein that has activity on certain neurons of the central nervous system and the peripheral nervous system; it helps to support the survival of existing neurons, and encourage the growth and differentiation of new neurons and synapses through axonal and dendritic sprouting. In the brain, it is active in the hippocampus, cortex, cerebellum, and basal forebrain — areas vital to learning, memory, and higher thinking. BDNF was the second neurotrophic factor to be characterized, after NGF and before neurotrophin-3.