Local circuit allowing hypothalamic control of hippocampal area CA2 activity and consequences for CA1
Abstract
The hippocampus is critical for memory formation. The hypothalamic supramammillary nucleus (SuM) sends long-range projections to hippocampal area CA2. While the SuM-CA2 connection is critical for social memory, how this input acts on the local circuit is unknown. Using mice, we found that SuM axon stimulation elicited mixed excitatory and inhibitory responses in area CA2 pyramidal neurons (PNs). Parvalbumin-expressing basket cells were largely responsible for the feedforward inhibitory drive of SuM over area CA2. Inhibition recruited by the SuM input onto CA2 PNs increased the precision of action potential firing both in conditions of low and high cholinergic tone. Furthermore, SuM stimulation in area CA2 modulated CA1 activity, indicating that synchronized CA2 output drives a pulsed inhibition in area CA1. Hence, the network revealed here lays basis for understanding how SuM activity directly acts on the local hippocampal circuit to allow social memory encoding.
Data availability
The data analysed for this study are included in the manuscript and supporting files. These are included in tables, and data file for figure 7.
Article and author information
Author details
Funding
RIKEN Brain Science Institute
- Thomas J McHugh
Ministry of Education, Culture, Sports, Science and Technology (19H05646)
- Thomas J McHugh
Ministry of Education, Culture, Sports, Science and Technology (19H05233)
- Thomas J McHugh
Agence Nationale de la Recherche (ANR-13-JSV4-0002-01)
- Rebecca Ann Piskorowski
Agence Nationale de la Recherche (ANR-18-CE37-0020-01)
- Rebecca Ann Piskorowski
Ville de Paris (Programme Emergences)
- Rebecca Ann Piskorowski
Brain and Behavior Research Foundation (NARSAD Young INvestigator Award)
- Rebecca Ann Piskorowski
Fondation pour la Recherche Médicale (FRM:FTD20170437387)
- Vincent Robert
Schizo-Oui
- Vincent Robert
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Katalin Toth, University of Ottawa, Canada
Ethics
Animal experimentation: All procedures involving animals were performed in accordance with institutional regulations (French Ministry of Research and Education protocol #12406-2016040417305913). Animal sample sizes were estimated using power tests with standard deviations and ANOVA values from pilot experiments. A 15 % failure rate was assumed to account for stereotaxic injection errors and slice preparation complications. Every effort was made to reduce animal suffering.
Version history
- Received: September 22, 2020
- Accepted: May 17, 2021
- Accepted Manuscript published: May 18, 2021 (version 1)
- Version of Record published: May 26, 2021 (version 2)
Copyright
© 2021, Robert 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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