Neuromodulators synaptic transmission

Only the first type of neurotransmitter release mediates the fast point-to-point synaptic transmission process at classical synapses (sometimes referred to as wiring transmission). All of the other types of neurotransmitter release effect one or another form of volume transmission whereby the neurotransmitter signal acts diffusely over more prolonged time periods (Agnati et al., 1995). Of these volume transmitter pathways, the time constants and volumes involved differ considerably. For example, diffusible neurotransmitters such as nitric oxide act relatively briefly in a localized manner, whereas at least some neuropeptides act on the whole brain, and can additionally act outside of it (i.e., function as hormones). There is an overlap between wiring and volume neurotransmission in that all classical neurotransmitters act as wiring transmitters via ionotropic receptors, and also act as volume transmitters via G-protein-coupled receptors. Moreover, neuromodulators in turn feed back onto classical synaptic transmission. 

Information transfer between two neurons or between neurons and effector cells involves the release of chemical substances, which then act on the target cell by binding to appropriate receptors embedded in the plasma membrane. This process, as originally described by Otto Loewi (Loewi 1921), is termed chemical neurotransmission and occurs at contact sites known as synapses. Neurotransmitters exert their effects via members of two major families of receptors ionotropic and metabotropic neurotransmitter receptors. Activation of ionotropic receptors leads to an increase in the ion conductance of the membrane within a time scale of milliseconds or even less, whereas activation of metabotropic receptors results in slow effects (within seconds or even minutes) which involve more or less complex signaling cascades. Accordingly, information transfer via ionotropic receptors is called fast synaptic transmission, whereas the slow counterpart is called neuromodulation (Kaczmarek and Levitan 1987). 

Proctolin appears to potentiate synaptic transmission in the central nervous system of the cockroach P. americana (37). Bursts of spike activity in the ventral nerve cord of this insect were elicited by mechanical stimulation of the cereal organs. In the presence of micromolar proctolin, the peak frequency and the duration of bursts were slowly, but significantly, increased. Carbacol, by comparison, caused an immediate enhancement of spontaneous activity, but potentiation of bursts was not observed. Thus, it was concluded that proctolin might function as a neuromodulator in the terminal ganglion. 

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