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An anterior hypothalamic circuit gates stress vulnerability.
Zachary T Pennington1, Alexa R LaBanca1, Shereen D Abdel-Raheim1
1Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai.
Biorxiv : the Preprint Server for Biology
|November 18, 2024
Summary
Prior stress exposure sensitizes the brain, making individuals more vulnerable to future stressors. The anterior hypothalamic nucleus (AHN) plays a key role in this heightened stress sensitivity.
Area of Science:
- Neuroscience
- Stress Research
- Brain Circuitry
Background:
- Previous adversity can increase vulnerability to subsequent stress.
- The brain circuits underlying this increased susceptibility are not well understood.
Purpose of the Study:
- To identify brain circuits functionally remodeled by prior adversity.
- To elucidate the role of the anterior hypothalamic nucleus (AHN) in stress vulnerability.
Main Methods:
- Unbiased whole-brain activity mapping in mice.
- In vivo Miniscope imaging of neuronal activity.
- Optogenetic manipulation of neuronal activity and circuits.
Main Results:
- Prior adversity heightened stress reactivity in the anterior hypothalamic nucleus (AHN).
- Increased functional connectivity was observed between the AHN and threat-related limbic networks.
- AHN neuronal activity encodes stressor valence, and its manipulation altered stress reactivity.
- Silencing amygdala inputs to the AHN blocked the effect of prior adversity on stress sensitivity.
Conclusions:
- The anterior hypothalamic nucleus (AHN) is critically involved in gating stress vulnerability.
- The AHN scales valence signals from the amygdala to modulate stress sensitivity.
- Understanding AHN function offers insights into stress-related disorders.
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