Neuromodulation (biology)

Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. This is in contrast to classical synaptic transmission, in which one presynaptic neuron directly influences a single postsynaptic partner. Neuromodulators secreted by a small group of neurons diffuse through large areas of the nervous system, affecting multiple neurons. Major neuromodulators in the central nervous system include dopamine, serotonin, acetylcholine, histamine, and norepinephrine.

Neuromodulation 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 cerebrospinal fluid (CSF), influencing (or "modulating") the activity of several other neurons in the brain. For this reason, some neurotransmitters are also considered to be neuromodulators, such as serotonin and acetylcholine.

Neuromodulation is often contrasted with classical fast synaptic transmission. In both cases the transmitter acts on local postsynaptic receptors, but in neuromodulation, the receptors are typically G-protein coupled receptors while in classical chemical neurotransmission, they are ligand-gated ion channels. Neurotransmission that involves metabotropic receptors (like G-protein linked receptors) often also involves voltage-gated ion channels, and is relatively slow. Conversely, neurotransmission that involves exclusively ligand-gated ion channels is much faster. A related distinction is also sometimes drawn between modulator and driver synaptic inputs to a neuron, but here the emphasis is on modulating ongoing neuronal spiking versus causing that spiking.

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.

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