Involvement of metabotropic glutamate receptors in the regulation of synaptic plasticity

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Pharma cological Research. Vol. 22. Supplem ent 2,1990

INVOLVEMENT OF METABOTROPIC GLUTAMATE RECEPTORS IN THE REGULATION OF SYNAPTIC PLASTICITY. F. Nicoletti. Institute of Pharmacology, University of Catania, Italy. Excitatory amino acid receptors have been classified into two major subtypes: "ionotropic" receptors, linked to membrane ion channels; and "metabotropic" receptors, coupled to polyphosphoinositide hydrolysis. Ionotropic receptors are in turn divided into NMDA and non-NMDA (AMPA- and kainatesensitive> receptors. Both NMDA and metabotropic receptors are highly functional during the early stages of postnatal life and are involved in the regulation of developmental platicity. AMPA- and kainate-sensitive receptors are predominant in mature neurons, where their activation generates excitatory postsynaptic potentials. Based on studies on LTP formation, we have hypothesized that a combined activation of NMDA and metabotropic receptors is required for the early and late induction of processes that enable the long-lasting increase in synaptic efficacy in response to specific afferent inputs. While activation of NMDA receptors is involved in the induction, metabotropic receptors may rather contribute to the late expression and/or maintenance of ~TP. It is consistent with this hypothesis that (i> LTP induction leads to a delayed increase in the PPI response to ibotenate or trans-ACPD; and LTP decays more rapidly if induced in the presence of 2-amino-4phosphonobutanoate , a selective antagonist of metabotropic receptors (Reymann and Matthies, Neurosci, Lett., 98, 166, 1989) . Protein kinase C (PKC > may be a In common target for NMDA and metabotropic receptors. particular, metabotropic receptors may support PKC activation during the late non-decremental component of LTP, a stage that is specifically sensitive to PKC inhibitors. Since polyphosphoinositides tightly interact with some of the major actin-binding proteins, the increased sensitivity of metabotropic receptors may also contribute to the changes in cytoskeleton dynamics and dendritic spine shape that occur during LTP formation.

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© 1990 The Italian Pharmacological Society