DIFFERENT TRAINING PROCEDURES RECRUIT EITHER ONE OR 2 CRITICAL PERIODS FOR CONTEXTUAL MEMORY CONSOLIDATION, EACH OF WHICH REQUIRES PROTEIN-SYNTHESIS AND PKA

We have used a combined genetic and pharmacological approach to define the time course of the requirement for protein kinase A (PKA) and pro tein synthesis in long-term memory for contextual fear conditioning in mice. The time course of amnesia in transgenic mice that express R(AB ) and have genetically reduced PKA activity in the hippocampus paralle ls that observed both in mice treated with inhibitors of PKA and mice treated with inhibitors of protein synthesis. This PKA- and protein sy nthesis-dependent memory develops between 1 hr and 3 hr after training . By injecting the protein synthesis inhibitor anisomycin or the PKA i nhibitor Rp-cAMPs at various times after training, we find that depend ing on the nature of training, contextual memory has either one or two brief consolidation periods requiring synthesis of new proteins, and each of these also requires PKA. Weak training shows two time periods of sensitivity to inhibitors of protein synthesis and PKA, whereas str onger training exhibits only one. These studies underscore the paralle l dependence of long-term contextual memory on protein synthesis and P KA and, suggest that different training protocols may recruit a common signaling pathway in distinct ways.