Activation of metabotropic glutamate receptors is necessary for long-term potentiation in the dentate gyrus and for spatial learning.

We have examined the effects of the metabotropic glutamate receptor antagonist (RS)-a-methyl-4-carboxyphenylglycine (MCPG) on performance in the water maze, and on LTP in the dentate gyrus, MCPG (5 mM) reversibly blocked the induction of LTP in the perforant path-granule cell projection when perfused into the dentate gyrus of the anaesthetized rat. When injected bilaterally into the lateral ventricles, MCPG (20 mM) disrupted the performance of rats in a spatial learning version of the water maze task. In a terminal experiment, when tetanic stimulation was given to the perforant path, LTP, was found to be significantly reduced in MCPG-injected rats compared to control rats injected with vehicle. These experiments indicate that activation of MCPG-sensitive metabotropic glutamate receptors is necessary both for the full expression of LTP and spatial learning, and supply further evidence for the hypothesis that LTP provides synaptic mechanism for certain forms of learning.