Synaptic Modulation Mediated by G-Protein-Coupled Presynaptic Receptors

Abstract

Synaptic transmission can be modulated by a variety of factors and for various lengths of time ranging from milliseconds to years. The efficacy of synaptic transmission can be modulated either by a change in the “sensitivity” of postsynaptic receptors or in the number of transmitter packets released by an action potential, the quantal content. Much effort has been made to identify the site of induction and expression of long-term synaptic modulation (i.e., synaptic plasticity) as the first step for elucidating the underlying molecular mechanism. At the presynaptic terminal, a variety of G-protein-coupled receptors are expressed and contribute to presynaptic modulation. Among them, metabotropic glutamate receptors (mGluRs) and GABA_B receptors are well known to suppress release of transmitters when activated by their ligands. Although the target of these presynaptic inhibitors were assumed to be either calcium channels, potassium channels, or the exocytotic machinery downstream of calcium influx, no direct evidence has been provided because of technical difficulties of recording from mammalian presynaptic terminals. A breakthrough in this situation was made recently by the development of a rodent brainstem slice preparation that has enabled us to record directly from presynaptic terminals with patch-clamp techniques.