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 synaptic transmission in which an axonal terminal secretes neurotransmitters to target fast-acting receptors of only one particular partner neuron. Neuromodulators are neurotransmitters that diffuse through neural tissue to affect slow-acting receptors of many neurons. Major neuromodulators in the central nervous system include dopamine, serotonin, acetylcholine, histamine, and norepinephrine. Neuromodulators are known to have modulatory effects on target areas such as decorrelation of spiking, increase of firing rate, sharpening of spatial tuning curves, maintenance of increased spiking during working memory.A neuromodulator 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.