PKC-GAMMA MUTANT MICE EXHIBIT MILD DEFICITS IN SPATIAL AND CONTEXTUALLEARNING

We are undertaking a genetic approach to investigate the role that syn aptic modulation in the mammalian central nervous system plays in lear ning and memory and to identify relevant molecular components. We have generated mice deficient in the gamma isoform of protein kinase C (PK Cgamma), an enzyme that has previously been implicated in both long-te rm potentiation (LTP) and learning and memory. These mice have a modif ied LTP of synaptic transmission in the hippocampus. We demonstrate th at PKCgamma-mutant mice can learn to carry out hippocampus-dependent t asks, although mild deficits are evident. Thus, hippocampal CA1 LTP in duced by the conventional tetanic stimulation is not essential for the mice to exhibit spatial and contextual learning. Furthermore, the mod ification of hippocampal synaptic plasticity correlates with the learn ing deficits we observe.