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 reconfiguring synaptic connectivity.[3]
Major neuromodulators in the central nervous system include: dopamine, serotonin, acetylcholine, histamine, norepinephrine, nitric oxide, and several neuropeptides. Cannabinoids can also be powerful CNS neuromodulators.[4][5][6] Neuromodulators can be packaged into vesicles and released by neurons, secreted as hormones and delivered through the circulatory system.[7] A neuromodulator can be conceptualized as a neurotransmitter 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 (CSF), influencing (or "modulating") the activity of several other neurons in the brain.[8]
^DeRiemer SA, Strong JA, Albert KA, Greengard P, Kaczmarek LK (24–30 January 1985). "Enhancement of calcium current in Aplysia neurones by phorbol ester and protein kinase C". Nature. 313 (6000): 313–316. Bibcode:1985Natur.313..313D. doi:10.1038/313313a0. PMID2578617. S2CID4230710.