Neuromodulation
Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (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: altering intrinsic firing activity,[1] increasing or decreasing voltage-dependent currents,[2] altering synaptic efficacy, increasing bursting activity[2] and reconfigurating synaptic connectivity.[3]
Major neuromodulators in the central nervous system include:
Neuromodulatory systems
The major
Most other neurotransmitters, on the other hand, e.g.
System | Origin[9] | Targets[9] | Effects[9] |
---|---|---|---|
Noradrenaline system | Locus coeruleus | Adrenergic receptors in:
|
|
Lateral tegmental field |
|||
Dopamine system | Dopamine pathways: | Dopamine receptors at pathway terminations. |
|
Serotonin system | caudal dorsal raphe nucleus | Serotonin receptors in:
|
|
rostral dorsal raphe nucleus | Serotonin receptors in:
| ||
Cholinergic system | Pedunculopontine nucleus and dorsolateral tegmental nuclei (pontomesencephalotegmental complex) | (mainly) M1 receptors in:
|
|
basal optic nucleus of Meynert |
(mainly) M1 receptors in:
| ||
medial septal nucleus |
(mainly) M1 receptors in:
|
Noradrenaline system
The noradrenaline system consists of around 15,000 neurons, primarily in the
Dopamine system
The dopamine or dopaminergic system consists of several pathways, originating from the
Parkinson's disease is at least in part related to dropping out of dopaminergic cells in deep-brain nuclei, primarily the melanin-pigmented neurons in the substantia nigra 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, for example, blocks the reuptake of dopamine, leaving these neurotransmitters in the synaptic gap for longer.
- deprenyl inhibits monoamine oxidase(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.
Serotonin pharmacology
- Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are widely used antidepressants that specifically block the reuptake of serotonin with less effect on other transmitters.[17][18][19]
- Monoamine oxidase inhibitors allow reuptake of biogenic amine neurotransmitters from the synapse, but inhibit an enzyme which normally destroys (metabolizes) some of the transmitters after their reuptake. More of the neurotransmitters (especially serotonin, noradrenaline and dopamine) are available for release into synapses. MAOIs take several weeks to alleviate the symptoms of depression.[17][19][21][22]
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.[17][19][22]
Cholinergic system
The cholinergic system consists of projection neurons from the
GABA
Neuropeptides
Neuropeptides 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.[25] Most neuropeptides bind to G-protein coupled receptors, however some neuropeptides directly gate ion channels or act through kinase receptors.
- Vasopressin
- Oxytocin
- Gastrin
- Cholecystokinins
- Somatostatin
- Cortistatins
- RF-amides
- Neuropeptide FF
- Neuropeptide Y -
- Pancreatic Polypeptide
- Peptide YY
- Prolactin-releasing peptide
- Calcitonin
- Adrenomedullin
- Natriuretic
- Bombesin-like peptides
- Endothelin
- Glucagon
- Secretin
- Vasoactive Intestinal Peptide
- Growth Hormone Releasing Hormone
- Gastric Inhibitory Peptide
- Corticotropin Releasing Hormone
- Urocortin
- Urotensin
- Substance P
- Neuromedins
- Tensin
- Kinin
- Granin
- Nerve Growth Factor
- Motilin
- Ghrelin
- Galanin
- Neuropeptide B/W
- Neurexophilin
- Insulin
- Relaxin
- Agouti-related protein homolog gene
- Prolactin
- Apelin
- Metastasis-suppressor
- Diazepam-binding inhibitor
- Cerebellins
- Leptin
- Adiponectin
- Visfatin
- Resistin
- Nucleibindin
- Ubiquitin
Neuromuscular systems
Neuromodulators may alter the output of a physiological system by acting on the associated inputs (for instance, central pattern generators). However, modeling work suggests that this alone is insufficient,[28] 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.[28]
Volume transmission
Neurotransmitter systems are systems of
Other uses
Neuromodulation also refers to an emerging class of medical therapies that target the nervous system for restoration of function (such as in
See also
- 5-HT2c receptor agonist
- Natural neuroactive substance
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