Neuromodulation is the

physiological Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...

process by which a given

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to

metabotropic A metabotropic receptor, also referred to by the broader term G-protein-coupled receptor, is a type of membrane receptor that initiates a number of metabolic steps to modulate cell activity. The nervous system utilizes two types of receptors: met ...

G-protein coupled receptors G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of protein family, evolution ...

(GPCRs) to initiate a second messenger signaling cascade that induces a broad, long-lasting signal. This modulation can last for hundreds of milliseconds to several minutes. Some of the effects of neuromodulators include: alter intrinsic firing activity, increase or decrease voltage-dependent currents, alter synaptic efficacy, increase bursting activity and reconfiguration of synaptic connectivity. Major neuromodulators in the central nervous system include:

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...

histamine Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discovered in ...

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...

nitric oxide Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its che ...

, and several

neuropeptide Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the ...

Cannabinoids Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...

can also be powerful CNS neuromodulators. Neuromodulators can be packaged into vesicles and released by neurons, secreted as hormones and delivered through the circulatory system. A neuromodulator can be conceptualized as a

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

that is not reabsorbed by the pre-synaptic neuron or broken down into a metabolite. Some neuromodulators end up spending a significant amount of time in the

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...

(CSF), influencing (or "modulating") the activity of several other neurons in the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

Neuromodulatory systems

The major

neurotransmitter systems A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotr ...

are the

noradrenaline Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...

(norepinephrine) system, the

system, the

system, and the

cholinergic Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word "choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cation. F ...

system. Drugs targeting the neurotransmitter of such systems affect the whole system, which explains the mode of action of many drugs. Most other neurotransmitters, on the other hand, e.g.

glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...

, GABA and

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...

, are used very generally throughout the central nervous system.

Noradrenaline system

The noradrenaline system consists of around 15,000 neurons, primarily in the

locus coeruleus The locus coeruleus () (LC), also spelled locus caeruleus or locus ceruleus, is a nucleus in the pons of the brainstem involved with physiological responses to stress and panic. It is a part of the reticular activating system. The locus coerule ...

. This is diminutive compared to the more than 100 billion neurons in the brain. As with dopaminergic neurons in the substantia nigra, neurons in the locus coeruleus tend to be

melanin Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino ...

-pigmented.

Noradrenaline Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...

is released from the neurons, and acts on

adrenergic receptor The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta ...

s. Noradrenaline is often released steadily so that it can prepare the supporting glial cells for calibrated responses. Despite containing a relatively small number of neurons, when activated, the noradrenaline system plays major roles in the brain including involvement in suppression of the neuroinflammatory response, stimulation of neuronal plasticity through LTP, regulation of glutamate uptake by astrocytes and LTD, and consolidation of memory.

Dopamine system

The dopamine or dopaminergic system consists of several pathways, originating from the

ventral tegmentum The ventral tegmental area (VTA) (tegmentum is Latin for ''covering''), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is the ...

substantia nigra The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. ''Substantia nigra'' is Latin for "black substance", reflecting the fact that parts of the substantia nigra app ...

as examples. It acts on

dopamine receptor Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through diffe ...

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

is at least in part related to dropping out of dopaminergic cells in deep-brain nuclei, primarily the melanin-pigmented neurons in the

but secondarily the noradrenergic neurons of the locus coeruleus. Treatments potentiating the effect of dopamine precursors have been proposed and effected, with moderate success.

Dopamine pharmacology

Cocaine Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...

, for example, blocks the

reuptake Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the pre-synaptic neuron at a synapse) or glial cell after it has performed its function of transm ...

, leaving these neurotransmitters in the synaptic gap longer. *

AMPT Alpha-methyl-''p''-tyrosine (AMPT) is a tyrosine hydroxylase enzyme inhibitor and is therefore a drug involved in inhibiting the Catecholamine#Biosynthesis, catecholamine biosynthetic pathway. AMPT inhibits tyrosine hydroxylase whose enzymatic act ...

prevents the conversion of tyrosine to

L-DOPA -DOPA, also known as levodopa and -3,4-dihydroxyphenylalanine, is an amino acid that is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize -DOPA ...

, the precursor to dopamine;

reserpine Reserpine is a drug that is used for the treatment of high blood pressure, usually in combination with a thiazide diuretic or vasodilator. Large clinical trials have shown that combined treatment with reserpine plus a thiazide diuretic reduces m ...

prevents dopamine storage within

vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...

; and

deprenyl Selegiline, also known as L-deprenyl and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. It is provided in the form of a capsule or ...

inhibits

monoamine oxidase Monoamine oxidases (MAO) () are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The first ...

(MAO)-B and thus increases dopamine levels.

Serotonin system

The serotonin created by the brain comprises around 10% of total body serotonin. The majority (80-90%) is found in the gastrointestinal (GI) tract. It travels around the brain along the

medial forebrain bundle The medial forebrain bundle (MFB), is a neural pathway containing axon, fibers from the basal olfactory regions, the periamygdaloid region and the septal nuclei, as well as fibers from brainstem regions, including the ventral tegmental area and nig ...

and acts on

serotonin receptors 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neur ...

. In the

peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain ...

(such as in the gut wall) serotonin regulates vascular tone.

Serotonin pharmacology

Selective serotonin reuptake inhibitors Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracell ...

(SSRIs) such as

fluoxetine Fluoxetine, sold under the brand names Prozac and Sarafem, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder, obsessive–compulsive disorde ...

are widely used antidepressants that specifically block the reuptake of serotonin with less effect on other transmitters. *

Tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...

also block reuptake of biogenic amines from the synapse, but may primarily effect serotonin or norepinephrine or both. They typically take 4 to 6 weeks to alleviate any symptoms of depression. They are considered to have immediate and long-term effects. *

Monoamine oxidase inhibitors Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, espec ...

allow reuptake of biogenic amine neurotransmitters from the synapse, but inhibit an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

which normally destroys (metabolizes) some of the transmitters after their reuptake. More of the neurotransmitters (especially

and

) are available for release into synapses. MAOIs take several weeks to alleviate the symptoms of depression. Although changes in neurochemistry are found immediately after taking these antidepressants, symptoms may not begin to improve until several weeks after administration. Increased transmitter levels in the synapse alone does not relieve the depression or anxiety.

Cholinergic system

The cholinergic system consists of projection neurons from the

pedunculopontine nucleus The pedunculopontine nucleus (PPN) or pedunculopontine tegmental nucleus (PPT or PPTg) is a collection of neurons located in the upper pons in the brainstem. It lies caudal to the substantia nigra and adjacent to the superior cerebellar peduncle. ...

laterodorsal tegmental nucleus The laterodorsal tegmental nucleus (or lateroposterior tegmental nucleus) is a nucleus situated in the brainstem, spanning the midbrain tegmentum and the pontine tegmentum. Its location is one-third of the way from the pedunculopontine nucleus to ...

, and

basal forebrain Part of the human brain, the basal forebrain structures are located in the forebrain to the front of and below the striatum. They include the ventral basal ganglia (including nucleus accumbens and ventral pallidum), nucleus basalis, diagonal band ...

and interneurons from the striatum and nucleus accumbens. It is not yet clear whether acetylcholine as a neuromodulator acts through

volume transmission Neuromodulation is the physiology, physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic receptor, metabotropic, G protein-coupled recep ...

or classical synaptic transmission, as there is evidence to support both theories. Acetylcholine binds to both metabotropic

muscarinic receptors Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rece ...

(mAChR) and the ionotropic

nicotinic receptors Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...

(nAChR). The cholinergic system has been found to be involved in responding to cues related to the reward pathway, enhancing signal detection and sensory attention, regulating homeostasis, mediating the stress response, and encoding the formation of memories.

GABA

Gamma-aminobutyric acid (GABA) has an inhibitory effect on brain and spinal cord activity.

Neuropeptides

Neuropeptide Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the ...

s are small proteins used for communication in the nervous system. Neuropeptides represent the most diverse class of signaling molecules. There are 90 known genes that encode human neuropeptide precursors. In invertebrates, there are ~50 known genes encoding neuropeptide precursors. Most neuropeptides bind to G-protein coupled receptors, however some neuropeptides directly gate ion channels or act through kinase receptors. *

Opioid peptides Opioid peptides are peptides that bind to opioid receptors in the brain; opiates and opioids mimic the effect of these peptides. Such peptides may be produced by the body itself, for example endorphins. The effects of these peptides vary, but th ...

– a large family of endogenous neuropeptides that are widely distributed throughout the central and peripheral nervous system. Opiate drugs such as

heroin Heroin, also known as diacetylmorphine and diamorphine among other names, is a potent opioid mainly used as a recreational drug for its euphoric effects. Medical grade diamorphine is used as a pure hydrochloride salt. Various white and brow ...

and

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...

act at the receptors of these neurotransmitters. #

Endorphins Endorphins (contracted from endogenous morphine) are chemical signals in the brain that block the perception of pain and increase feelings of wellbeing. They are produced and stored in an area of the brain known as the pituitary gland. Hist ...

Enkephalin An enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, as they are internally derived and bind to the body's opioid receptors. Discovered in 1975, two forms of enkephalin ...

s #

Dynorphin Dynorphins (Dyn) are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 (PC2), multiple active peptides are released: dynorphin A, dynorphin B, a ...

s *

Vasopressin Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travel ...

Oxytocin Oxytocin (Oxt or OT) is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. It plays a role in social bonding, reproduction, childbirth, and the period after childbirth. Oxytocin ...

Gastrin Gastrin is a peptide hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas. Gastrin ...

Cholecystokinin Cholecystokinin (CCK or CCK-PZ; from Greek ''chole'', "bile"; ''cysto'', "sac"; ''kinin'', "move"; hence, ''move the bile-sac (gallbladder)'') is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and ...

s *

Somatostatin Somatostatin, also known as growth hormone-inhibiting hormone (GHIH) or by several other names, is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G protein-couple ...

Cortistatins The cortistatins are a group of steroidal alkaloids first isolated in 2006 from the marine sponge '' Corticium simplex''. The cortistatins were first discovered in a search for naturally occurring compounds that inhibit proliferation of human um ...

* RF-amides *

Neuropeptide FF NPFF Neuropeptide FF (FLFQPQRFa) is a mammalian amidated neuropeptide originally isolated from bovine brain and characterized as a pain-modulating peptide, with anti-opioid activity on morphine-induced analgesia. In humans, Neuropeptide FF pepti ...

Neuropeptide Y 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 ma ...

- *

Pancreatic Polypeptide Pancreatic polypeptide (PP) is a polypeptide secreted by PP cells in the endocrine pancreas. It regulates pancreatic secretion activities, and also impacts liver glycogen storage and gastrointestinal secretion. Its secretion may be impacted by ...

Peptide YY Peptide YY (PYY) also known as peptide tyrosine tyrosine is a peptide that in humans is encoded by the gene. Peptide YY is a short (36-amino acid) peptide released from cells in the ileum and colon in response to feeding. In the blood, gut, a ...

Prolactin-releasing peptide Prolactin-releasing peptide (PrRP) is a peptide hormone that in humans is encoded by the ''PRLH'' gene. PrRP stimulates prolactin (PRL) release and regulates the expression of prolactin through binding to the prolactin-releasing peptide receptor ( ...

Calcitonin Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates. in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the ...

Adrenomedullin Adrenomedullin (ADM or AM) is a vasodilator peptide hormone of uncertain significance in human health and disease. It was initially isolated in 1993 from a pheochromocytoma, a tumor of the adrenal medulla: hence the name. In humans ADM is encoded ...

Natriuretic Natriuresis is the process of sodium excretion in the urine through the action of the kidneys. It is promoted by ventricular and atrial natriuretic peptides as well as calcitonin, and inhibited by chemicals such as aldosterone. Natriuresis lowers ...

* Bombesin-like peptides *

Endothelin Endothelins are peptides with receptor (biochemistry), receptors and effects in many body organs. Endothelin constricts blood vessels and raises blood pressure. The endothelins are normally kept in balance by other mechanisms, but when gene ex ...

Glucagon Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medicati ...

Secretin Secretin is a hormone that regulates water homeostasis throughout the body and influences the environment of the duodenum by regulating secretions in the stomach, pancreas, and liver. It is a peptide hormone produced in the S cells of the duode ...

Vasoactive Intestinal Peptide Vasoactive intestinal peptide, also known as vasoactive intestinal polypeptide or VIP, is a peptide hormone that is vasoactive in the intestine. VIP is a peptide of 28 amino acid residues that belongs to a glucagon/secretin superfamily, the ligan ...

* Growth Hormone Releasing Hormone *

Gastric Inhibitory Peptide Glucose-dependent insulinotropic polypeptide (GIP), also known as Gastric inhibitory polypeptide or gastric inhibitory peptide (also abbreviated as GIP), is an inhibiting hormone of the secretin family of hormones. While it is a weak inhibitor ...

Corticotropin Releasing Hormone Corticotropin-releasing hormone (CRH) (also known as corticotropin-releasing factor (CRF) or corticoliberin; corticotropin may also be spelled corticotrophin) is a peptide hormone involved in stress responses. It is a releasing hormone that belo ...

Urocortin Urocortin is a protein that in humans is encoded by the ''UCN'' gene. Urocortin belongs to the corticotropin-releasing factor (CRF) family of proteins which includes CRF, urotensin I, sauvagine, urocortin II and urocortin III. Urocortin is invol ...

* Urotensin *

Substance P Substance P (SP) is an undecapeptide (a peptide composed of a chain of 11 amino acid residues) and a member of the tachykinin neuropeptide family. It is a neuropeptide, acting as a neurotransmitter and as a neuromodulator. Substance P and its clos ...

* Neuromedins * Tensin *

Kinin A kinin is any of various structurally related polypeptides, such as bradykinin and kallidin. They are members of the autacoid family. Kinins are peptides that are cleaved from kininogens by the process of kallikreins. Kallikreins activate kinins wh ...

Granin Granin (chromogranin and secretogranin) is a protein family of regulated secretory proteins ubiquitously found in the cores of amine and peptide hormone and neurotransmitter dense-core secretory vesicles. Function Granins (chromogranins or sec ...

Nerve Growth Factor Nerve growth factor (NGF) is a neurotrophic factor and neuropeptide primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons. It is perhaps the prototypical growth factor, in that it was on ...

Motilin Motilin is a 22-amino acid polypeptide hormone in the motilin family that, in humans, is encoded by the ''MLN'' gene. Motilin is secreted by endocrine Mo cells (also referred to as M cells, which are not the same as the M cells, or microfold ce ...

Ghrelin Ghrelin (; or lenomorelin, INN) is a hormone produced by enteroendocrine cells of the gastrointestinal tract, especially the stomach, and is often called a "hunger hormone" because it increases the drive to eat. Blood levels of ghrelin are highe ...

Galanin Galanin is a neuropeptide encoded by the ''GAL'' gene, that is widely expressed in the brain, spinal cord, and gut of humans as well as other mammals. Galanin signaling occurs through three G protein-coupled receptors. Much of galanin's function ...

* Neuropeptide B/W * Neurexophilin *

Insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...

Relaxin Relaxin is a protein hormone of about 6000 Da first described in 1926 by Frederick Hisaw. The relaxin family peptide hormones belong to the insulin superfamily and consists of seven peptides of high structural but low sequence similarity; rela ...

* Agouti-related protein homolog gene *

Prolactin Prolactin (PRL), also known as lactotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secreted from the pit ...

Apelin Apelin (also known as APLN) is a peptide that in humans is encoded by the ''APLN'' gene. Apelin is one of two endogenous ligands for the G-protein-coupled APJ receptor that is expressed at the surface of some cell types. It is widely expressed i ...

* Metastasis-suppressor * Diazepam-binding inhibitor * Cerebellins *

Leptin Leptin (from Ancient Greek, Greek λεπτός ''leptos'', "thin" or "light" or "small") is a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps to regulate Energy homeostasis, energy balance by inhib ...

Adiponectin Adiponectin (also referred to as GBP-28, apM1, AdipoQ and Acrp30) is a protein hormone and adipokine, which is involved in regulating glucose levels as well as fatty acid breakdown. In humans it is encoded by the ''ADIPOQ'' gene and it is produced ...

* Visfatin *

Resistin Resistin also known as adipose tissue-specific secretory factor (ADSF) or C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein (XCP1) is a cysteine-rich peptide hormone derived from adipose tissue that in humans is encoded by th ...

* Nucleibindin *

Ubiquitin Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fo ...

Neuromuscular systems

Neuromodulators may alter the output of a physiological system by acting on the associated inputs (for instance,

central pattern generator Central pattern generators (CPGs) are self-organizing biological neural circuits that produce rhythmic outputs in the absence of rhythmic input. They are the source of the tightly-coupled patterns of neural activity that drive rhythmic and stereot ...

s). However, modeling work suggests that this alone is insufficient, because the neuromuscular transformation from neural input to muscular output may be tuned for particular ranges of input. Stern et al. (2007) suggest that neuromodulators must act not only on the input system but must change the transformation itself to produce the proper contractions of muscles as output.

Volume transmission

Neurotransmitter systems are systems of

neurons A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

in the brain expressing certain types of

neurotransmitters A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neur ...

, 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.

Other uses

Neuromodulation also refers to an emerging class of medical therapies that target the nervous system for restoration of function (such as in

cochlear implants A cochlear implant (CI) is a surgically implanted neuroprosthesis that provides a person who has moderate-to-profound sensorineural hearing loss with sound perception. With the help of therapy, cochlear implants may allow for improved speech unde ...

), relief of pain, or control of symptoms, such as tremor seen in movement disorders like

. The therapies consist primarily of targeted electrical stimulation, or infusion of medications into the cerebrospinal fluid using intrathecal drug delivery, such as

baclofen Baclofen, sold under the brand name Lioresal among others, is a medication used to treat muscle spasticity such as from a spinal cord injury or multiple sclerosis. It may also be used for hiccups and muscle spasms near the end of life. It is ta ...

for

spasticity Spasticity () is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity, and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles. ...

. Electrical stimulation devices include

deep brain stimulation Deep brain stimulation (DBS) is a neurosurgical procedure involving the placement of a medical device called a neurostimulator, which sends electrical impulses, through implanted electrodes, to specific targets in the brain (the brain nucleu ...

systems (DBS), colloquially referred to as "brain pacemakers",

spinal cord stimulator A spinal cord stimulator (SCS) or dorsal column stimulator (DCS) is a type of implantable neuromodulation device (sometimes called a "pain pacemaker") that is used to send electrical signals to select areas of the spinal cord (dorsal columns) for ...

s (SCS) and vagus nerve stimulators (VNS), which are implanted using minimally invasive procedures, or

transcutaneous electrical nerve stimulation Transcutaneous electrical nerve stimulation (TENS or TNS) is the use of electric current produced by a device to stimulate the nerves for therapeutic purposes. TENS, by definition, covers the complete range of transcutaneously applied currents ...

devices, which are fully external, among others.

References

External links

North American Neuromodulation Society North American Neuromodulation Society is a professional scientific organization that serves to promote and advance neuromodulation as a treatment for various diseases. The majority of its members work in pain-related disciplines, although membe ...

Neuromodulation and Neural PlasticityInternational Neuromodulation SocietyScolarpedia article on neuromodulation
{{Rhombencephalon Neurochemistry Neurophysiology