GENETIC DEMONSTRATION OF A ROLE FOR PKA IN THE LATE-PHASE OF LTP AND IN HIPPOCAMPUS-BASED LONG-TERM-MEMORY

To explore the role of protein kinase A (PKA) in the late phase of lon g-term potentiation (L-LTP) and memory, we generated transgenic mice t hat express R(AB), an inhibitory form of the regulatory subunit of PKA , only in the hippocampus and other forebrain regions by using the pro moter from the gene encoding Ca2+/calmodulin protein kinase II alpha. In these R(AB) transgenic mice, hippocampal PKA activity was reduced, and L-LTP was significantly decreased in area CA1, without affecting b asal synaptic transmission or the early phase of LTP. Moreover, the L- LTP deficit was paralleled by behavioral deficits in spatial memory an d in long-term but not short-term memory for contextual fear condition ing. These deficits in long-term memory were similar to those produced by protein synthesis inhibition. Thus, PKA plays a critical role in t he consolidation of long-term memory.