Metabotropic glutamate receptors: electrophysiological properties and role in plasticity

Electrophysiological research on mGluRs is now very extensive, and it is clear that activation of mGluRs results in a large number of diverse cellular actions. Studies of mGluRs and on ionic channels has clearly demonstrated that mGluR activation has a widespread and potent inhibitory action on both voltage-gated Ca2+ channels and K+ channels. Inhibition of N-type Ca2+ channels, and inhibition of Ca(++)-dependent K+ current, IAHP, and IM being particularly prominent. Potentiation of activation of both Ca2+ and K+ channels has also been observed, although less prominently than inhibition, but mGluR-mediated activation of non-selective cationic channels is widespread. In a small number of studies, generation of an mGluR-mediated slow excitatory postsynaptic potential has been demonstrated as a consequence of the effect of mGluR activation on ion channels, such as activation of a non-selective cationic channels. Although certain mGluR-modulation of channels is a consequence of direct G-protein-linked action, for example, inhibition of Ca2+ channels, many other effects occur as a result of activation of intracellular messenger pathways, but at present, little progress has been made on the identification of the messengers. The field of study of the involvement of mGluRs in synaptic plasticity is very large. Evidence for the involvement of mGluRs in one form of LTD induction in the cerebellum and hippocampus is now particularly impressive. However, the role of mGluRs in LTP induction continues to be a source of dispute, and resolution of the question of the exact involvement of mGluRs in the induction of LTP will have to await the production of more selective ligands and of selective gene knockouts.