Hippocampal-hypothalamic circuit controls context-dependent innate defensive responses
Abstract
Preys use their memory - where they sensed a predatory threat and whether a safe shelter is nearby - to dynamically control their survival instinct to avoid harm and reach safety. However, it remains unknown which brain regions are involved, and how such top-down control of innate behaviour is implemented at the circuit level. Here, using adult male mice, we show that the anterior hypothalamic nucleus (AHN) is best positioned to control this task as an exclusive target of the hippocampus (HPC) within the medial hypothalamic defense system. Selective optogenetic stimulation and inhibition of hippocampal inputs to the AHN revealed that the HPC→AHN pathway not only mediates the contextual memory of predator threats but also controls the goal-directed escape by transmitting information about the surrounding environment. These results reveal a new mechanism for experience-dependent, top-down control of innate defensive behaviours.
Data availability
Numerical data used to generate Figures 1-8 and Extended data figures 1-12 are provided in the Figure Source Data files that correspond to figure labels. Custom written MATLAB code is uploaded on Zenodo. (10.5281/zenodo.5899428)
Article and author information
Author details
Funding
Canadian Institute of Health Research (507489)
- Junchul Kim
NSERC Discovery (506730)
- Junchul Kim
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 were approved by the Local Animal Care Committee (LACC) at University of Toronto. AUP2011332.
Reviewing Editor
- Mario Penzo, National Institute of Mental Health, United States
Version history
- Preprint posted: August 9, 2021 (view preprint)
- Received: October 15, 2021
- Accepted: April 13, 2022
- Accepted Manuscript published: April 14, 2022 (version 1)
- Version of Record published: April 26, 2022 (version 2)
- Version of Record updated: May 9, 2022 (version 3)
Copyright
© 2022, Bang 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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