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Entorhinal cortex layer III input to the hippocampus is crucial for temporal association memory.

Associating temporally discontinuous elements is crucial for the formation of episodic and working memories that depend on the hippocampal-entorhinal network. However, the neural circuits subserving these associations have remained unknown. The layer III inputs of the entorhinal cortex to the hippocampus may contribute to this process. To test this hypothesis, we generated a transgenic mouse in which these inputs are specifically inhibited. The mutant mice displayed significant impairments in spatial working-memory tasks and in the encoding phase of trace fear-conditioning. These results indicate a critical role of the entorhinal cortex layer III inputs to the hippocampus in temporal association memory.

Pubmed ID: 22052975


  • Suh J
  • Rivest AJ
  • Nakashiba T
  • Tominaga T
  • Tonegawa S


Science (New York, N.Y.)

Publication Data

December 9, 2011

Associated Grants

  • Agency: NIMH NIH HHS, Id: P50-MH58880
  • Agency: NIMH NIH HHS, Id: R01-MH078821

Mesh Terms

  • Animals
  • Association Learning
  • CA1 Region, Hippocampal
  • Conditioning (Psychology)
  • Electric Stimulation
  • Entorhinal Cortex
  • Fear
  • Hippocampus
  • Male
  • Maze Learning
  • Memory, Short-Term
  • Mental Recall
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Pathways
  • Synaptic Transmission