Instruct: Given a question, retrieve passages that can help answer the question.
Query: What is the most abundant neurotransmitter in the human brain?
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".
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.
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).
The MAOIs work by inhibiting the monoamine oxidase enzymes that, as the name suggests, break down the monoamine neurotransmitters. This leads to increased concentrations of most of the monoamine neurotransmitters in the human brain, serotonin, norepinephrine, dopamine and melatonin. The fact that they are more efficacious than the newer generation antidepressants is what leads scientists to develop newer antidepressants that target a greater range of neurotransmitters. The problem with MAOIs is that they have many potentially dangerous side-effects such as hypotension, and there is a risk of food and drug interactions that can result in potentially fatal serotonin syndrome or a hypertensive crisis. Although selective MAOIs can reduce, if not eliminate these risks, their efficacy tends to be lower.
Glutamine is the most abundant naturally occurring, nonessential amino acid in the human body, and one of the few amino acids that can directly cross the blood–brain barrier. Humans obtain glutamine through catabolism of proteins in foods they eat. In states where tissue is being built or repaired, like growth of babies, or healing from wounds or severe illness, glutamine becomes conditionally essential.
Fatty acids play an important role in normal brain development as well as maintaining proper neuronal function. It has been found that certain fatty acids that are in abundance in the brain may be linked with FFA1. These fatty acids likely activate FFA1, inducing an intracellular response. It has been found that docosahexaenoic acid (DHA) has a higher affinity than other fatty acids for FFA1. DHA makes up 30% and arachidonic acid, another fatty acid found in the brain, makes up 20% of the fatty acids in the brain. Both of these fatty acids must be obtained from the diet because the body cannot make them. A correct balance of these fatty acids is vital to normal brain function and structure. DHA is supplied to the brain via astrocytes, which release DHA so that it reaches a high enough concentration to act as an extracellular signal on FFA1.
The scientific study of the nervous system increased significantly during the second half of the twentieth century, principally due to advances in molecular biology, electrophysiology, and computational neuroscience. This has allowed neuroscientists to study the nervous system in all its aspects: how it is structured, how it works, how it develops, how it malfunctions, and how it can be changed. For example, it has become possible to understand, in much detail, the complex processes occurring within a single neuron. Neurons are cells specialized for communication. They are able to communicate with neurons and other cell types through specialized junctions called synapses, at which electrical or electrochemical signals can be transmitted from one cell to another. Many neurons extrude a long thin filament of axoplasm called an axon, which may extend to distant parts of the body and are capable of rapidly carrying electrical signals, influencing the activity of other neurons, muscles, or glands at their termination points. A nervous system emerges from the assemblage of neurons that are connected to each other.
The adrenal medulla is at the centre of each adrenal gland, and is surrounded by the adrenal cortex. The chromaffin cells of the medulla are the body's main source of the catecholamines adrenaline and noradrenaline, released by the medulla. Approximately 20% noradrenaline (norepinephrine) and 80% adrenaline (epinephrine) are secreted here.
Amino acids are organic compounds containing amine (-NH) and carboxyl (-COOH) functional groups, along with a side chain (R group) specific to each amino acid. The key elements of an amino acid are carbon (C), hydrogen (H), oxygen (O), and nitrogen (N), although other elements are found in the side chains of certain amino acids. About 500 naturally occurring amino acids are known (though only 20 appear in the genetic code) and can be classified in many ways. They can be classified according to the core structural functional groups' locations as alpha- (α-), beta- (β-), gamma- (γ-) or delta- (δ-) amino acids; other categories relate to polarity, pH level, and side chain group type (aliphatic, acyclic, aromatic, containing hydroxyl or sulfur, etc.). In the form of proteins, amino acid residues form the second-largest component (water is the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis.
Dopamine does not cross the blood–brain barrier, so its synthesis and functions in peripheral areas are to a large degree independent of its synthesis and functions in the brain. A substantial amount of dopamine circulates in the bloodstream, but its functions there are not entirely clear. Dopamine is found in blood plasma at levels comparable to those of epinephrine, but in humans, over 95% of the dopamine in the plasma is in the form of dopamine sulfate, a conjugate produced by the enzyme sulfotransferase 1A3/1A4 acting on free dopamine. The bulk of this dopamine sulfate is produced in the mesentery that surrounds parts of the digestive system. The production of dopamine sulfate is thought to be a mechanism for detoxifying dopamine that is ingested as food or produced by the digestive process—levels in the plasma typically rise more than fifty-fold after a meal. Dopamine sulfate has no known biological functions and is excreted in urine.
The neuroscientist Donald Hebb (1904–1985) was the first to distinguish between short-term memory and long-term memory. According to current theories in neuroscience, things that we "notice" are stored in short-term memory for up to a few minutes; this memory depends on "reverberating" electrical activity in neuronal circuits, and is very easily destroyed by interruption or interference. Memories stored for longer than this are stored in "long-term memory". Whether information is stored in long-term memory depends on its "importance"; for any animal, memories of traumatic events are potentially important for the adaptive value that they have for future avoidance behavior, and hormones that are released during stress have a role in determining what memories are preserved. In humans, traumatic stress is associated with acute secretion of epinephrine and norepinephrine (adrenaline and noradrenaline) from the adrenal medulla and cortisol from the adrenal cortex. Increases in these facilitate memory, but chronic stress associated with prolonged hypersecretion of cortisol may have the opposite effect. The limbic system is involved in memory storage and retrieval as well as giving emotional significance to sensory inputs. Within the limbic system, the hippocampus is important for explicit memory, and for memory consolidation; it is also sensitive to stress hormones, and has a role in recording the emotions of a stressful event. The amygdala may be particularly important in assigning emotional values to sensory inputs.
Due to more recent Medical, Rehabilitation and ongoing results 'neuroplasticity' within the mechanics of our brains lead to re-arrangement of the brain's workings. These often result in the synapses arranging alternate routes, to achieve previous habits. Neuroplasticity is the brain's ability to reorganise itself by forming new neural connections throughout life. Neuroplasticity allows the neurons (nerve cells) in the brain to compensate for injury and disease and to adjust their activities in response to new situations or to changes in their environment.
Some 400 genes are shown to be brain-specific. In all neurons, ELAVL3 is expressed, and in pyramidal neurons, NRGN and REEP2 are also expressed. GAD1 – essential for the biosynthesis of the neurotransmitter GABA – is expressed in interneurons. Proteins expressed in glial cells are astrocyte markers GFAP, and S100B. Myelin basic protein, and the transcription factor, OLIG2 are expressed in oligodendrocytes.
It appears to play a role in a wide variety of autonomic functions, such as regulating blood pressure and heart rate.
Thewissen’s current work involves counting neurons in bowhead and beluga whale brain samples, to assess brain function, in Utqiagvik—formerly Barrow—Alaska. Though the size of the brains of sperm whales and killer whales are larger than those of any other organism, including humans, a better measure of brain function is to determine how many neurons there are in the brain. Suzana Herculano-Houzel has developed a method of counting of neurons of human and other animals' brains and the relation between the cerebral cortex area and thickness and number of cortical folds. Humans and other primates pack about twice the number of neurons in a cubed inch of brain as most other mammals.
G protein-coupled receptors (GPCRs), also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors (GPLR), comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal transduction pathways and, ultimately, cellular responses. G protein-coupled receptors are found only in eukaryotes, including yeast, choanoflagellates, and animals. The ligands that bind and activate these receptors include light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters, and vary in size from small molecules to peptides to large proteins. G protein-coupled receptors are involved in many diseases, and are also the target of approximately 30% of all modern medicinal drugs.
The body's physical arousal response (vaginal lubrication and engorgement of the clitoris in women and erection in men) occurs due to two separate pathways which normally work together: psychogenic and reflex. Arousal due to fantasies, visual input, or other mental stimulation is a psychogenic sexual experience, and arousal resulting from physical contact to the genital area is reflexogenic. In psychogenic arousal, messages travel from the brain via the spinal cord to the nerves in the genital area. The psychogenic pathway is served by the spinal cord at levels T11–L2. Thus people injured above the level of the T11 vertebra do not usually experience psychogenic erection or vaginal lubrication, but those with an injury below T12 can. Even without these physical responses, people with SCI often feel aroused, just as uninjured people do. The ability to feel the sensation of a pinprick and light touch in the dermatomes for T11–L2 predicts how well the ability to have psychogenic arousal is preserved in both sexes. Input from the psychogenic pathway is sympathetic, and most of the time it sends inhibitory signals that prevent the physical arousal response; in response to sexual stimulation, excitatory signals are increased and inhibition is reduced. Removing the inhibition that is normally present allows the spinal reflexes that trigger the arousal response to take effect.
The endocrine system is a chemical messenger system consisting of hormones, the group of glands of an organism that secrete those hormones directly into the circulatory system to regulate the function of distant target organs, and the feedback loops which modulate hormone release so that homeostasis is maintained. In humans, the major endocrine glands are the thyroid gland and the adrenal glands. In vertebrates, the hypothalamus is the neural control center for all endocrine systems. The study of the endocrine system and its disorders is known as endocrinology. Endocrinology is a branch of internal medicine.
Microglia are a collective type of neuroglia (glial cell) located throughout the brain and spinal cord., found to have 9 distinct subtypes with different functions, appearance, and presence. Microglia account for 10–15% of all cells found within the brain. As the resident macrophage cells, they act as the first and main form of active immune defense in the central nervous system (CNS). Microglia (and other neuroglia including astrocytes) are distributed in large non-overlapping regions throughout the CNS. Microglia are key cells in overall brain maintenance—they are constantly scavenging the CNS for plaques, damaged or unnecessary neurons and synapses, and infectious agents. Since these processes must be efficient to prevent potentially fatal damage, microglia are extremely sensitive to even small pathological changes in the CNS. This sensitivity is achieved in part by the presence of unique potassium channels that respond to even small changes in extracellular potassium.
Kathleen Montagu (estimated birth between 1847 and 1907 – 28 March 1966) was the first researcher to identify dopamine in human brains. 
Working in Hans Weil-Malherbe’s laboratory at the Runwell Hospital outside London the presence of dopamine was identified by paper chromatography in the brain of several species, including a human brain. Her research was published in August 1957, followed and confirmed by Hans Weil-Malherbe in November 1957.
The Nobel laureate, Bengt I. Samuelsson, and colleagues first described 5("S")-HETE in 1976 as a metabolite of arachidonic acid made by rabbit neutrophils. Biological activity was linked to it several years later when it was found to stimulate human neutrophil rises in cytosolic calcium, chemotaxis, and increases in their cell surface adhesiveness as indicated by their aggregation to each other. Since a previously discovered arachidonic acid metabolite made by neutrophils, leukotriene B4 (LTB), also stimulates human neutrophil calcium rises, chemotaxis, and auto-aggregation and is structurally similar to 5("S")-HETE in being a 5-("S")-hydroxy-eicosateraenoate, it was assumed that 5-("S")-HETE stimulated cells through the same cell surface receptors as those used by (LTB) viz., the leukotriene B4 receptors. However, further studies in neutrophils indicated that 5-("S")-HETE acts through a receptor distinct from that used by LTB as well as various other neutrophil stimuli. This 5("S")-HETE receptor is termed the oxoeicosanoid receptor 1 (abbreviated as (OXER1).
Neuropeptide Y (NPY) is a 36 amino-acid neuropeptide that is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems. NPY has been identified as the most abundant peptide present in the mammalian central nervous system, which consists of the brain and spinal cord. It is secreted alongside other neurotransmitters such as GABA and glutamate.
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.
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.
Kaitocephalin acts by inhibiting glutamate receptors. Glutamate is the most abundant neurotransmitter in the vertebrate nervous system and is involved in learning, memory, and neuroplasticity. It is an excitatory neurotransmitter, so binding of glutamate to its receptors increases ion flow through the postsynaptic membrane. Excess glutamate can lead to cell death and neurological damage through a phenomenon called excitotoxicity. Excitotoxicity occurs when calcium ion influx creates a positive feedback loop, leading to breakdown of the cell membrane and apoptosis. This process is part of the ischemic cascade, when low blood supply (ischemia) causes a series of events leading to cell death; this is the mechanism by which strokes cause brain damage. High levels of glutamate have also been linked to the neuronal degeneration observed in Alzheimer's disease, Parkinson's disease, and epilepsy.