Different Training Procedures Recruit Either One or Two Critical Periods for Contextual Memory Consolidation, Each of Which Requires Protein Synthesis and PKA

TLDR

The development of contextual fear memory depends on protein synthesis and PKA activity in the hippocampus, with amnesia occurring within 1–3 h after training, mirroring the effects of pharmacological inhibitors. The study aims to delineate the temporal requirement of PKA and protein synthesis for long‑term contextual fear memory in mice. Using timed injections of anisomycin or Rp‑cAMPs after training, the authors mapped brief consolidation windows that depend on new protein synthesis and PKA activity. Weak training produces two brief consolidation windows sensitive to protein synthesis and PKA inhibition, whereas stronger training elicits only one, highlighting that distinct training protocols engage the same signaling pathway in different temporal patterns.

Abstract

We have used a combined genetic and pharmacological approach to define the time course of the requirement for protein kinase A (PKA) and protein 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 parallels that observed both in mice treated with inhibitors of PKA and mice treated with inhibitors of protein synthesis. This PKA- and protein synthesis-dependent memory develops between 1 hr and 3 hr after training. By injecting the protein synthesis inhibitor anisomycin or the PKA inhibitor Rp-cAMPs at various times after training, we find that depending 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 stronger training exhibits only one. These studies underscore the parallel dependence of long-term contextual memory on protein synthesis and PKA and suggest that different training protocols may recruit a common signaling pathway in distinct ways.