Activation of Entorhinal Cortical Projections to the Dentate Gyrus Underlies Social Memory Retrieval

Cell Rep. 2018 May 22;23(8):2379-2391. doi: 10.1016/j.celrep.2018.04.073.


Social interactions are essential to our mental health, and a deficit in social interactions is a hallmark characteristic of numerous brain disorders. Various subregions within the medial temporal lobe have been implicated in social memory, but the underlying mechanisms that tune these neural circuits remain unclear. Here, we demonstrate that optical activation of excitatory entorhinal cortical perforant projections to the dentate gyrus (EC-DG) is necessary and sufficient for social memory retrieval. We further show that inducible disruption of p21-activated kinase (PAK) signaling, a key pathway important for cytoskeletal reorganization, in the EC-DG circuit leads to impairments in synaptic function and social recognition memory, and, importantly, optogenetic activation of the EC-DG terminals reverses the social memory deficits in the transgenic mice. These results provide compelling evidence that activation of the EC-DG pathway underlies social recognition memory recall and that PAK signaling may play a critical role in modulating this process.

Keywords: brain disorder; dentate gyrus; entorhinal cortex; optogenetics; p21-activated kinase; social recognition memory; synaptic transmission; tetracycline inducible system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dentate Gyrus / drug effects
  • Dentate Gyrus / physiology*
  • Entorhinal Cortex / drug effects
  • Entorhinal Cortex / physiology*
  • Mental Recall / drug effects
  • Mental Recall / physiology*
  • Mice, Transgenic
  • Optogenetics
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • Recognition, Psychology / drug effects
  • Signal Transduction / drug effects
  • Social Behavior*
  • Synaptic Transmission / drug effects
  • p21-Activated Kinases / antagonists & inhibitors
  • p21-Activated Kinases / metabolism


  • Protein Kinase Inhibitors
  • p21-Activated Kinases