A genetic test of the effects of mutations in PKA on mossy fiber LTP and its relation to spatial and contextual learning

Using a genetic approach, we assessed the effects of mutations in protein kinase A (PKA) on long-term potentiation (LTP) in the messy fiber pathway and its relationship to spatial and contextual learning. Ablation by gene targeting of the C beta(1) or the RI beta isoform of PKA produces a selective defect in messy fiber LTP, providing genetic evidence for the role of these isoforms in the messy fiber pathway. Despite the elimination of messy fiber LTP, the behavioral responses to novelty, spatial learning, and conditioning to context are unaffected. Thus, contrary to current theories about hippocampal function, messy fiber LTP does not appear to be required for spatial or contextual learning. In the absence of messy fiber LTP, adequate spatial and contextual information might reach the CA1 region via other pathways from the entorhinal cortex.