Mechanisms of memory-supporting neuronal dynamics in hippocampal area CA3

Cell. 2024 Nov 27;187(24):6804-6819.e21. doi: 10.1016/j.cell.2024.09.041. Epub 2024 Oct 24.

Abstract

Hippocampal CA3 is central to memory formation and retrieval. Although various network mechanisms have been proposed, direct evidence is lacking. Using intracellular Vm recordings and optogenetic manipulations in behaving mice, we found that CA3 place-field activity is produced by a symmetric form of behavioral timescale synaptic plasticity (BTSP) at recurrent synapses among CA3 pyramidal neurons but not at synapses from the dentate gyrus (DG). Additional manipulations revealed that excitatory input from the entorhinal cortex (EC) but not the DG was required to update place cell activity based on the animal's 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. Theoretical analyses further highlight the superior memory storage capacity of such networks, especially when dealing with correlated input patterns. This evidence elucidates the cellular and circuit mechanisms of learning and memory formation in the hippocampus.

Keywords: BTSP; CA3; attractor dynamics; hippocampus; memory; place cell; synaptic plasticity.

MeSH terms

  • Animals
  • CA3 Region, Hippocampal* / cytology
  • CA3 Region, Hippocampal* / physiology
  • Dentate Gyrus / cytology
  • Dentate Gyrus / physiology
  • Entorhinal Cortex* / cytology
  • Entorhinal Cortex* / physiology
  • Male
  • Memory* / physiology
  • Mice
  • Mice, Inbred C57BL
  • Models, Neurological
  • Neuronal Plasticity* / physiology
  • Neurons / physiology
  • Optogenetics
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / physiology
  • Synapses / metabolism
  • Synapses / physiology