# Conditioned social fear, the prefrontal cortex, and bed nucleus of the stria terminalis

> **NIH NIH R15** · UNIVERSITY OF COLORADO DENVER · 2020 · $463,838

## Abstract

Summary Social fear is a learned behavior and can be adaptive, but heightened social fear is frequently a
component of anxiety-related disorders such as social anxiety disorder (SAD) or post-traumatic stress disorder
(PTSD). Fear responses, both learned and innate, are made up of a continuum of adaptive behaviors and
these defensive responses become maladaptive in anxiety disorders. We have developed a novel conditioned
social fear paradigm in rats in which a footshock unconditioned stimulus (US) is paired with a social stimulus (a
novel same-sex conspecific) as the conditioning stimulus (CS). Then, we re-expose the experimental animal to
the CS rat the next day in a different context and assess social and escape behaviors in an escapable social
interaction test (ESIT) that we have developed. We have observed that a session of conditioned social fear
using our procedure produces increased avoidance behavior in the ESIT as well as increased aggressive
behavior. The overall objective of this AREA proposal is to determine the neural circuitry involved in the
alterations in social behavior produced by conditioned social fear in male and female rats. We will focus on the
medial prefrontal cortex (mPFC) to bed nucleus of the stria terminalis (BNST) neuronal pathway. The BNST
has been implicated in fear and anxiety and receives substantial input from the mPFC (Wood et al., 2018).
Two primary subregions of the mPFC, the prelimbic cortex (PL) and the infralimbic cortex (IL) both project to
the BNST, which is increasingly appreciated as a regulator of fear and anxiety. We propose that learned social
fear/anxiety depends on the mPFC  BNST neurocircuit and that the PL and IL inputs are separately involved
in the distinct phases of social fear learning and memory: acquisition and extinction. We will use a cre-
dependent intersectional chemogenetic approach to systematically inhibit or activate PL or IL neurons that
project to the BNST, and we will test for alterations in social behavior (largely ignored in studies of fear and
anxiety) in the ESIT as our dependent measure. We will also measure neuroplasticity-related proteins in this
neural pathway using immunohistochemistry. These experiments will be the first to explore the contribution of
the mPFC  BNST circuitry in learned social fear/anxiety. Understanding the neural pathways involved in
these phenomena will be valuable in the treatment of anxiety disorders that include a social component, such
as SAD and PTSD. We propose to achieve our objectives with 2 Specific Aims. Aim 1 seeks to determine
whether PL  BNST neurons mediate acquisition of conditioned social fear. Aim 2 seeks to determine
whether IL  BNST neurons mediate extinction of conditioned social fear.

## Key facts

- **NIH application ID:** 9880260
- **Project number:** 1R15HD100824-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Sondra T Bland
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $463,838
- **Award type:** 1
- **Project period:** 2020-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9880260

## Citation

> US National Institutes of Health, RePORTER application 9880260, Conditioned social fear, the prefrontal cortex, and bed nucleus of the stria terminalis (1R15HD100824-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9880260. Licensed CC0.

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