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Pharmacological antagonism of metabotropic glutamate receptor 1 regulates long‐term potentiation and spatial reference memory in the dentate gyrus of freely moving rats via N ‐methyl‐ d ‐aspartate and metabotropic glutamate receptor‐dependent mechanisms
Author(s) -
Naie Katja,
ManahanVaughan Denise
Publication year - 2005
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2005.03864.x
Subject(s) - long term potentiation , dentate gyrus , metabotropic glutamate receptor , perforant path , neuroscience , synaptic plasticity , ltp induction , metabotropic receptor , long term depression , hippocampal formation , glutamate receptor , metabotropic glutamate receptor 1 , hippocampus , schaffer collateral , perforant pathway , chemistry , metabotropic glutamate receptor 5 , psychology , medicine , receptor , ampa receptor
Group I metabotropic glutamate receptors (mGluRs) are critically required for multiple forms of hippocampal synaptic plasticity in vivo . The role of the receptor subtype mGluR1 in long‐term potentiation (LTP) and learning is unclear. We examined the contribution of mGluR1 to hippocampal LTP and spatial learning using the selective antagonist (S)‐(+)‐α‐amino‐4carboxy‐2‐methylbenzene‐acetic acid (LY367385). Male Wistar rats were chronically implanted with recording and stimulating electrodes to enable measurement of evoked potentials from medial perforant path–dentate gyrus granule cell synapses. An injection cannula was inserted into the ipsilateral cerebral ventricle to enable drug application. Experiments were begun 10 days after the implantation procedure. We induced a robust LTP which lasted over 25 h with a 200‐Hz tetanization. Injections of LY367385 at all concentrations under investigation (4–32 nmol in a 5‐µL injection volume) did not affect basal synaptic transmission. In contrast, we observed a dose‐dependent impairment of LTP expression: LY367385 (4 nmol) had no effect on LTP induction, whereas 8 and 16 nmol LY367385 reduced both LTP induction and expression, suggestive of an interaction with N ‐methyl‐ d ‐aspartate receptors. We assessed the effects of daily LY367385 application (8 nmol) on performance in an eight‐arm radial maze. LY367385‐treated rats showed deficits in reference but not working memory performance compared with vehicle‐treated controls. Rearing, grooming and locomotor activity were unaffected by LY367385. These data suggest an important role for mGluR1 in LTP and learning and highlight the specific significance of this mGluR subtype for reference memory.