Ventral hippocampal projections to the medial prefrontal cortex regulate social memory

Abstract
Data availability
Article and author information
Metrics

Abstract

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.

Data availability

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

Article and author information

Author details

Mary L Phillips

Department of Neurobiology, University of Alabama at Birmingham, Birmingham, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-4696-1555
Holly Anne Robinson

Department of Neurobiology, University of Alabama at Birmingham, Birmingham, United States

Competing interests
The authors declare that no competing interests exist.
Lucas Pozzo-Miller

Department of Neurobiology, University of Alabama at Birmingham, Birmingham, United States

For correspondence
lucaspm@uab.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-6085-5527

Funding

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.

Ethics

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).

Copyright

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.