PKC-GAMMA MUTANT MICE EXHIBIT MILD DEFICITS IN SPATIAL AND CONTEXTUAL LEARNING

We are undertaking a genetic approach to investigate the role that synaptic modulation in the mammalian central nervous system plays in learning and memory and to identify relevant molecular components. We have generated mice deficient in the gamma isoform of protein kinase C (PKCgamma), an enzyme that has previously been implicated in both long-term potentiation (LTP) and learning and memory. These mice have a modified LTP of synaptic transmission in the hippocampus. We demonstrate that PKCgamma-mutant mice can learn to carry out hippocampus-dependent tasks, although mild deficits are evident. Thus, hippocampal CA1 LTP induced by the conventional tetanic stimulation is not essential for the mice to exhibit spatial and contextual learning. Furthermore, the modification of hippocampal synaptic plasticity correlates with the learning deficits we observe.