Mechanisms of memory storage and retrieval in hippocampal area CA3

Abstract

Hippocampal area CA3 is thought to play a central role in memory formation and retrieval. Although various network mechanisms have been hypothesized to mediate these computations, direct evidence is lacking. Using intracellular membrane potential recordings from CA3 neurons and optogenetic manipulations in behaving mice we found that place field activity is produced by a symmetric form of Behavioral Timescale Synaptic Plasticity (BTSP) at recurrent synaptic connections among CA3 principal neurons but not at synapses from the dentate gyrus (DG). Additional manipulations revealed that excitatory input from the entorhinal cortex (EC) but not DG was required to update place cell activity based on the animals movement. These data were captured by a computational model that used BTSP and an external updating input to produce attractor dynamics under online learning conditions. Additional theoretical results demonstrate the enhanced memory storage capacity of such networks, particularly in the face of correlated input patterns. The evidence sheds light on the cellular and circuit mechanisms of learning and memory formation in the hippocampus. One Sentence SummaryEvidence from behaving mice points to cellular and circuit mechanisms that underlie observed attractor dynamics in area CA3.