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Ventral hippocampal projections to the medial prefrontal cortex regulate social memory

  1. Mary L Phillips
  2. Holly Anne Robinson
  3. Lucas Pozzo-Miller  Is a corresponding author
  1. University of Alabama at Birmingham, United States
Research Article
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Cite this article as: eLife 2019;8:e44182 doi: 10.7554/eLife.44182


Inputs from the ventral hippocampus (vHIP) to the medial prefrontal cortex (mPFC) are implicated in several neuropsychiatric disorders. Here, we show that the vHIP-mPFC projection is hyperactive in the Mecp2 knockout mouse model of the autism spectrum disorder Rett syndrome, which has deficits in social memory. Long-term excitation of mPFC-projecting vHIP neurons in wild-type mice impaired social memory, whereas their long-term inhibition in Rett mice rescued social memory deficits. The extent of social memory improvement was negatively correlated with vHIP-evoked responses in mPFC slices, on a mouse-per-mouse basis. Acute manipulations of the vHIP-mPFC projection affected social memory in a region and behavior selective manner, suggesting that proper vHIP-mPFC signaling is necessary to recall social memories. In addition, we identified an altered pattern of vHIP innervation of mPFC neurons, and increased synaptic strength of vHIP inputs onto layer 5 pyramidal neurons as contributing factors of aberrant vHIP-mPFC signaling in Rett mice.

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All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Mary L Phillips

    Department of Neurobiology, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4696-1555
  2. Holly Anne Robinson

    Department of Neurobiology, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Lucas Pozzo-Miller

    Department of Neurobiology, University of Alabama at Birmingham, Birmingham, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6085-5527


NIH Office of the Director (R56-NS103089-01A1)

  • Lucas Pozzo-Miller

Civitan International (Civitan Emerging Scholar: W John Rynearson Award)

  • Mary L Phillips

International Rett Syndrome Foundation

  • Lucas Pozzo-Miller

NIH Office of the Director (T32-NS061788-04)

  • Mary L Phillips

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.


Animal experimentation: Mice were handled and housed according to the Committee on Laboratory Animal Resources of the National Institutes of Health. All experimental protocols were reviewed and approved annually by the Institutional Animals Care and Use Committee of the University of Alabama at Birmingham (IACUC-20114).

Reviewing Editor

  1. Lisa M Monteggia, Vanderbilt University, United States

Publication history

  1. Received: December 6, 2018
  2. Accepted: May 17, 2019
  3. Accepted Manuscript published: May 21, 2019 (version 1)
  4. Version of Record published: May 30, 2019 (version 2)


© 2019, Phillips et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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