A specific role for group I mGluRs in hippocampal LTP and hippocampus-dependent spatial learning

Metabotropic glutamate receptors (mGluRs) have been implicated in long-term potentiation and in learning and memory formation. In this study, we teste d the effects of group I mGluR inhibition on synaptic plasticity and learni ng of rats at different levels of organization (1) in the hippocampal slice preparation; (2) in freely moving animals implanted with chronic hippocamp al electrodes; and (3) in different spatial learning paradigms. To allow a direct comparison of the effects obtained the same doses were used in all p aradigms. Bath-application of the selective group I mGluR antagonist (S)4-c arboxyphenylglycine (4-CPG) impaired a decremental long-term potentiation ( LTP) induced by a weak tetanization paradigm, but failed to affect a robust LTP generated by strong tetanization. In contrast, 4-CPG impaired a robust LTP in freely moving animals if applied 30 min before tetanization. The sa me dose of 4-CPG only impeded spatial learning mildly in the eight-arm radi al maze and had no effect on a simple configuration of the Y-maze spatial a lternation task. In the more difficult configuration of this task, however, 4-CPG caused complete amnesia. The lack of state-dependent 4-CPG actions a nd the absence of any 4-CPG effects in the open-field test classify the obt ained retention deficit as a selective impairment of memory storage. Our re sults indicate a specific role of group I mGluRs in certain types of synapt ic plasticity and of spatial learning.