neuromodulation 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: alter intrinsic firing activity, increase or decrease voltage-dependent currents, alter synaptic efficacy, increase bursting activity and reconfiguration of synaptic connectivity. for the therapy, see neuromodulation (medicine). for other uses, see neuromodulation (disambiguation). 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. neuromodulators can be packaged into vesicles and released by neurons, secreted as hormones and delivered through the circulatory system. 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. neuromodulatory systems