Parallel instabilities of long-term potentiation, place cells, and learning caused by decreased protein kinase A activity

To further elucidate the links among synaptic plasticity, hippocampal place cells, and spatial memory, place cells were recorded from wild-type mice a nd transgenic "R(AB)" mice with reduced forebrain protein kinase A (PKA) ac tivity after introduction into a novel environment. Place cells in both str ains were similar during the first exposure and were equally stable for rec ording sessions separated by 1 hr. Place cell stability in wild-type mice w as unchanged for sessions separated by 24 hr but was reduced in R(AB) mice over the longer interval. This stability pattern parallels both the reduced late-phase long-term potentiation in hippocampal slices from R(AB) mice an d the amnesia for context fear conditioning seen in R(AB) mice 24 but not 1 hr after training. The similar time courses of synaptic, network, and beha vioral instability suggest that the genetic reduction of PKA activity is re sponsible for the defects at each level and support the idea that hippocamp al synaptic plasticity is important in spatial memory.