GLUTAMATE-DEPENDENT MECHANISMS IN THE INDUCTION OF A CALCIUM LONG-TERM POTENTIATION-LIKE PHENOMENON

The electric synaptic efficacy, in terms of extracellular electrical p otentials, and the intracellular postsynaptic efficacy, in terms of in ositol phosphate (IP) accumulation, were evaluated in rat hippocampal slices exposed for a brief period (10 min) to a high concentration of calcium (+2.7 mM). In addition, the effects of N-methyl-D-asparate (NM DA) ionotropic and metabotropic glutamate receptor (mGluR) antagonists on the induction and the establishment or maintenance of enhanced syn aptic efficacy of CA1 pyramidal neurons due to high-calcium exposure w ere also tested. Elevation of the calcium concentration from 1.3-4 mM in the medium bathing hippocampal slices produced a long-lasting (60 o ver 90 min) increase in the slope of the CAI somatic excitatory postsy naptic potential and the amplitude of the population spike (PS). Slice perfusion with NMDA antagonists cyclazocine and cis-4-phosphonomethyl -2-piperidine-carboxylic acid (CGS 19755) or with mGluR antagonists L- 2-amino-3-phosphonopropionic acid (AP3) or alpha-methyl-4-carboxypheny l-glycine (all 0.1 mM), during the 10-min period of exposure to high-c alcium prevented the induction of such changes. By contrast, slice per fusion with the same concentration of CGS 19755 or L-AP3 did not affec t the already established long-lasting increase in amplitude of CA1 PS induced by high-calcium. Moreover, high-calcium failed to produce any significant modification of the basal IP accumulation or of the IP ac cumulation elicited by mGluR agonist 1S,3R-trans-amino cyclo-pentane-1 ,3-dicarboxylic acid (ACPD). In conclusion, the results confirm that h igh-calcium induces a long-lasting increase in synaptic efficacy in ra t hippocampal slices. Both NMDA ionotropic and mGluR receptors are inv olved in the induction, but not in the maintenance, of this phenomenon . In line with these data no modifications of basal or ACPD-induced ph osphoinositide hydrolysis have been found during the maintenance stage . Copyright (C) 1996 Elsevier Science Inc.