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NOBEL PRIZE 2026

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NIHNATIONAL INSTITUTE OF MENTAL HEALTH

Neural circuit mechanisms in social extinction of conditioned place avoidance

Completed
Institution
Baylor College of Medicine, TX
Principal investigator
Daoyun Ji
Funding
$200K
Duration
2024–2026
Open portfolio

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Abstract

PROJECT SUMMARY Excessive fear and avoidance is a hallmark of anxiety disorders including post-traumatic stress disorder and special phobia. Social support is commonly used in anxiety-disorder therapies to facilitate extinction of fear or avoidance. However, how neural activities inside the brain give rise to the social effects on extinction is unknown. Here we propose to study the underlying neural circuits in rats performing a specially designed behavioral task, called social extinction of conditioned place avoidance. In this task, a rat fear-conditioned to a shock-zone in an open arena learns from a conspecific rat that the place is no longer aversive, leading to a reduction of avoidance to the shock-zone. We will focus on the hippocampus (HP), given its key role in place coding and fear extinction, and the anterior cingulate cortex (ACC), given its crucial role in social learning. By conducting high-density tetrode recordings of HP and ACC neurons during this task, we will test a functional model that specifies how these neurons computationally contribute to social extinction of place avoidance. We will focus on how the hippocampal spatial representation of the shock-zone is activated by a social subject and how the ACC activities responding to the aversive experience at the shock-zone are dynamically altered during the extinction. In addition, we will determine a causal link between the HP and ACC neural activities and the social extinction behavior by closed-loop electrical and optogenetic manipulations. The outcomes of this study will provide a specific neural circuit mechanism for how social extinction is achieved inside the brain. The knowledge generated in this study may inspire novel strategies for better social support or intervention in anxiety disorders.

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NATIONAL INSTITUTE OF MENTAL HEALTHR21Biobehavioral Regulation, Learning and Ethology Study Section[BRLE]placeavoidanceanxiety disordersextinctionfearaccaversiveconditioned

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