A SPECIFIC ROLE FOR GROUP II METABOTROPIC GLUTAMATE RECEPTORS IN HIPPOCAMPAL LONG-TERM DEPRESSION AND SPATIAL MEMORY

Activity-dependent and sustained alterations in synaptic efficacy are widely regarded as the cellular correlates underlying learning and memory. Metabotropic glutamate receptors (mGluRs) are intrinsically involved in both hippocampal synaptic plasticity and spatial learning. Group 11 mGIuRs are required for persistent hippocampal long-term depression (LTD), but are not required for long-term potentiation (LTP) in the hippocampal CAI region in vivo. The role of these receptors in spatial learning, and in synaptic plasticity in the dentate gyrus in vivo has not yet been the subject of close scrutiny. We investigated the effects of group II mGIuR antagonism on LTP and LTD in the adult rat, at medial perforant path-dentate gyrus synapses, and on spatial learning in the eight-arm radial maze. Daily application of the group 2 mGIuR antagonist (2S)-alpha-ethylglutamic acid (EGLU) resulted in impairment of long-term (reference) memory with effects becoming apparent 6 days after training and drug-treatment began. Short-term (working) memory was unaffected throughout the 10-day study. Acute injection of EGLU did not affect either LTD or LTP in the dentate gyrus in vivo. Following six daily applications of EGLU a clear impairment of LTD but not LTP was apparent however. These data support that prolonged antagonism of group 11 mGIuRs results in an impairment of LTD that parallels the appearance of spatial memory deficits arising from group 11 mGIuR antagonism. These findings support the importance of group II mGIuRs for spatial memory formation and offer a further link between LTD and the encoding of spatial information in the hippocampus. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.