Local circuit allowing hypothalamic control of hippocampal area CA2 activity and consequences for CA1
- Institute of Psychiatry and Neuroscience of Paris, INSERM UMRS1266, France
- Institute of Psychiatry and Neuroscience of Paris, INSERM UMRS1266; GHU PARIS psychiatrie & neurosciences, France
- RIKEN Center for Brain Science, Japan
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
Rebecca Ann Piskorowski
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.
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.
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.
Metrics
-
- 2,981
- views
-
- 463
- downloads
-
- 32
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Local circuit allowing hypothalamic control of hippocampal area CA2 activity and consequences for CA1
eLife 10:e63352.
https://doi.org/10.7554/eLife.63352
Further reading
-
- Neuroscience
Studying infant minds with movies is a promising way to increase engagement relative to traditional tasks. However, the spatial specificity and functional significance of movie-evoked activity in infants remains unclear. Here, we investigated what movies can reveal about the organization of the infant visual system. We collected fMRI data from 15 awake infants and toddlers aged 5–23 months who attentively watched a movie. The activity evoked by the movie reflected the functional profile of visual areas. Namely, homotopic areas from the two hemispheres responded similarly to the movie, whereas distinct areas responded dissimilarly, especially across dorsal and ventral visual cortex. Moreover, visual maps that typically require time-intensive and complicated retinotopic mapping could be predicted, albeit imprecisely, from movie-evoked activity in both data-driven analyses (i.e. independent component analysis) at the individual level and by using functional alignment into a common low-dimensional embedding to generalize across participants. These results suggest that the infant visual system is already structured to process dynamic, naturalistic information and that fine-grained cortical organization can be discovered from movie data.
-
- Neuroscience
Outcomes can vary even when choices are repeated. Such ambiguity necessitates adjusting how much to learn from each outcome by tracking its variability. The medial prefrontal cortex (mPFC) has been reported to signal the expected outcome and its discrepancy from the actual outcome (prediction error), two variables essential for controlling the learning rate. However, the source of signals that shape these coding properties remains unknown. Here, we investigated the contribution of cholinergic projections from the basal forebrain because they carry precisely timed signals about outcomes. One-photon calcium imaging revealed that as mice learned different probabilities of threat occurrence on two paths, some mPFC cells responded to threats on one of the paths, while other cells gained responses to threat omission. These threat- and omission-evoked responses were scaled to the unexpectedness of outcomes, some exhibiting a reversal in response direction when encountering surprising threats as opposed to surprising omissions. This selectivity for signed prediction errors was enhanced by optogenetic stimulation of local cholinergic terminals during threats. The enhanced threat-evoked cholinergic signals also made mice erroneously abandon the correct choice after a single threat that violated expectations, thereby decoupling their path choice from the history of threat occurrence on each path. Thus, acetylcholine modulates the encoding of surprising outcomes in the mPFC to control how much they dictate future decisions.
