Molecular and systems mechanisms of memory consolidation and storage.
Until recently, memory consolidation and storage had been traditionally viewed as a permissive process derived from learning-activated molecular signaling cascades which include activations of the NMDA receptors, CaMKII, PKC, PKA and other kinases, new protein synthesis and CREB-mediated gene expression, and subsequent structural modifications at certain synapses. However, the time-scale of such a cascade is incompatible with the timescale of systems-level memory consolidation. Furthermore, increasing evidence suggests that synaptic proteins and structures are not stationary, but rather are highly dynamical and subjected to metabolic turnovers which would cause drift in synaptic efficacy and subsequently unstable neural circuits. Recent experiments using inducible gene- or protein-knockout techniques reveal that post-learning NMDA receptor and CaMKII reactivations are required for the systems-level consolidation of both hippocampal-dependent and hippocampal-independent memories. Furthermore, the reactivations of the NMDA receptors are also necessary for the long-term storage of old memories in the neural circuits. Therefore, the NMDA receptor reactivation-mediated synaptic reentry reinforcement (SRR) process may represent the unifying cellular mechanism in linking the consolidation and storage of long-term memories from the molecular level to the systems-level.
Wang
Huimin
H
Shanghai Institute of Brain Functional Genomics, The Key Laboratories of MOE and SSTC, East China Normal University, Shanghai 200062, China.
Hu
Yinghe
Y
Tsien
Joe Z
JZ
D000818:Animals; D001245:Association Learning / Q000502:physiology*; D006801:Humans; D008568:Memory / Q000502:physiology*; D008959:Models, Neurological; D009473:Neuronal Plasticity / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012054:Reinforcement, Psychology; D012153:Retention, Psychology; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate