Interregional synaptic maps among engram cells underlie memory formation

Science. 2018 Apr 27;360(6387):430-435. doi: 10.1126/science.aas9204.


Memory resides in engram cells distributed across the brain. However, the site-specific substrate within these engram cells remains theoretical, even though it is generally accepted that synaptic plasticity encodes memories. We developed the dual-eGRASP (green fluorescent protein reconstitution across synaptic partners) technique to examine synapses between engram cells to identify the specific neuronal site for memory storage. We found an increased number and size of spines on CA1 engram cells receiving input from CA3 engram cells. In contextual fear conditioning, this enhanced connectivity between engram cells encoded memory strength. CA3 engram to CA1 engram projections strongly occluded long-term potentiation. These results indicate that enhanced structural and functional connectivity between engram cells across two directly connected brain regions forms the synaptic correlate for memory formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / cytology
  • CA1 Region, Hippocampal / physiology*
  • CA3 Region, Hippocampal / cytology
  • CA3 Region, Hippocampal / physiology*
  • Conditioning, Classical
  • Fear
  • Green Fluorescent Proteins / analysis
  • HEK293 Cells
  • Humans
  • Long-Term Potentiation
  • Male
  • Memory / physiology*
  • Mice, Inbred C57BL
  • Neuroimaging / methods
  • Neuronal Plasticity
  • Neurons / physiology*
  • Synapses / physiology*


  • Green Fluorescent Proteins