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In neuroscience, neuromodulation is the process in which several classes of neurotransmitters in the nervous system regulate diverse populations of neurons. As opposed to direct synaptic transmission in which one presynaptic neuron directly influences a postsynaptic partner, neuromodulatory transmitters secreted by a small group of neurons diffuse through large areas of the nervous system, having an effect on multiple neurons. Examples of neuromodulators include dopamine, serotonin, acetylcholine, histamine and others.
A neuromodulator is a relatively new concept in the field and it can be conceptualized as a neurotransmitter that is not reabsorbed by the pre-synaptic neuron or broken down into a metabolite. Such neuromodulators end up spending a significant amount of time in the CSF (cerebrospinal fluid) and influencing (or modulating) the overall activity level of the brain. For this reason, some neurotransmitters are also considered as neuromodulators. Examples of neuromodulators in this category are serotonin and acetylcholine
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, 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.
Diffuse modulatory neurotransmitter systems
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.
The major neurotransmitter systems are the noradrenaline (norepinephrine) system, the dopamine system, the serotonin system and the cholinergic system. Drugs targeting the neurotransmitter of such systems affects the whole system, and explains the mode of action of many drugs.
|System||Origin|| Targets|| Effects|
|Noradrenaline system||locus coeruleus||adrenergic receptors in:||
|Lateral tegmental field|
|Dopamine system||dopamine pathways:||Dopamine receptors at pathway terminations.||motor system, reward system, cognition, endocrine, nausea|
|Serotonin system||caudal dorsal raphe nucleus||Serotonin receptors in:||Increase (introverson), mood, satiety, body temperature and sleep, while decreasing nociception.|
|rostral dorsal raphe nucleus||Serotonin receptors in:|
|Cholinergic system||pontomesencephalotegmental complex||(mainly) M1 receptors in:|
|basal optic nucleus of Meynert||(mainly) M1 receptors in:|
|medial septal nucleus||(mainly) M1 receptors in:|
Further reading: Norepinephrine#Norepinephrine system
The noradrenaline system consists of just 1500 neurons on each side of the brain, which is diminutive compared to the total amount of more than 100 billion neurons in the brain. Nevertheless, when activated, the system plays major roles in the brain, as seen in table above. Noradrenaline is released from the neurons, and acts on adrenergic receptors.
Further reading: Dopamine#Functions in the brain
Parkinson's disease is at least in part related to failure of dopaminergic cells in deep-brain nuclei, for example the substantia nigra. Treatments potentiating the effect of dopamine precursors have been proposed and effected, with moderate success.
- Cocaine, for example, blocks the reuptake of dopamine, leaving these neurotransmitters in the synaptic gap longer.
- AMPT prevents the conversion of tyrosine to L-DOPA, the precursor to dopamine; reserpine prevents dopamine storage within vesicles; and deprenyl inhibits monoamine oxidase (MAO)-B and thus increases dopamine levels.
Further reading: Serotonin#Gross anatomy
The serotonin system system contains only 1% of total body serotonin, the rest being found as transmitters in the peripheral nervous system. It travels around the brain along the medial forebrain bundle and acts on serotonin receptors. In the peripheral nervous system (such as in the gut wall) serotonin regulates vascular tone.
- Prozac is a selective serotonin reuptake inhibitor (SSRI), hence potentiating the effect of naturally released serotonin.
Further reading: Acetylcholine#in CNS
The gamma-aminobutyric acid (GABA) system is more generally distributed throughout the brain. Nevertheless, it has an overall inhibitory effect.
- Opioid peptides - these substances block nerve impulse generation in the secondary afferent pain neurons. These peptides are called opioid peptides because they have opium-like activity. The types of opioid peptides are:
- Substance P
Neuromodulation also refers to a medical procedure used to alter nervous system function for relief of pain. It consists primarily of electrical stimulation, lesioning of specific regions of the nervous system, or infusion of substances into the cerebrospinal fluid. Electrical stimulation are devices such as Spinal Cord Stimulators (SCS) (surgically implanted) or Transcutaneous Electrical Nerve Stimulators (TENS) (external device).
- ↑ 1.0 1.1 Stern, E, Fort TJ, Millier MW, Peskin CS, Brezina V (2007). Decoding modulation of the neuromuscular transform. Neurocomputing (6954).
- ↑ 2.0 2.1 2.2 Unless else specified in boxes, then ref is: Rang, H. P. (2003). Pharmacology, page 474 for noradrenaline system, page 476 for dopamine system, page 480 for serotonin system and page 483 for cholinergic system., Edinburgh: Churchill Livingstone.
- North American Neuromodulation Society
- Neuromodulation and Neural Plasticity
- International Neuromodulation Society
Cell physiology: cell signaling
|Types of proteins|
Human brain: forebrain (cerebrum · cerebral cortex · cerebral hemispheres, grey matter) (TA A14.1.09.002–240, 301–320, GA 9.818–826)
| Some categorizations are approximations, and some Brodmann areas span gyri.
cerebral peduncle: midbrain tegmentum (periaqueductal gray, ventral tegmentum, nucleus raphe dorsalis), pretectum, substantia nigra, red nucleus, pedunculopontine nucleus, medial longitudinal fasciculus, medial lemniscus, rubrospinal tract, lateral lemniscus
Brain: rhombencephalon (hindbrain)
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