# Title: The thalamic nucleus reuniens mediates the transition from reactive to proactive defensive behavior via feedforward inhibition

> **NIH NIH R03** · TEXAS A&M UNIVERSITY · 2022 · $71,727

## Abstract

PROJECT SUMMARY/ABSTRACT
 Life often requires us to be proactive in the face of danger. When crossing the road, the adaptive
response to the horn of an oncoming care is to cross to the other side as quickly as possible. Yet fear
can have an immobilizing effect, creating a paradoxical situation in which a deeply engrained defense
against danger must be suppressed in order to achieve safety. Thus, adaptive coping in a complex
environment necessitates the ability to move past defensive reactions in favor of proactive, problem-
solving behavioral strategies.
 Signaled active avoidance (SAA) is a behavioral conditioning paradigm that effectively models
the process by which a learned, problem-solving action replaces the innate reactions elicited by a
threatening cue. Past work suggests that the nucleus reuniens of the midline thalamus plays a crucial
role in this process, acting to suppress immobilizing responses in favor of an adaptive behavioral
strategy that prevents an aversive outcome. Work proposed here will extend this finding by using
chemogenetic techniques to target the crucial outputs of the reuniens that function to suppress freezing
and facilitate active avoidance. Our primary hypothesis is that projections from the nucleus reuniens
engage feedforward inhibition by activating inhibitory interneurons in limbic regions, such as the ventral
hippocampus and the basolateral amygdala, that mediate the expression of aversive associative
memory and thus conditioned freezing. Successful execution of the proposed studies will establish an
important neural mechanism that promotes behavioral flexibility and adaptive problem solving under
threat.
 A proactive style of coping is associated with an internal locus of control and resilience,
suggesting the mental health relevance of its underlying circuitry. By dissecting the function of this
pathway, our goal is to generate preclinical data that hastens clinical advancement by providing targets
for cutting-edge therapeutic innovations.

## Key facts

- **NIH application ID:** 10354461
- **Project number:** 1R03MH128654-01
- **Recipient organization:** TEXAS A&M UNIVERSITY
- **Principal Investigator:** Justin M Moscarello
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $71,727
- **Award type:** 1
- **Project period:** 2021-12-10 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10354461

## Citation

> US National Institutes of Health, RePORTER application 10354461, Title: The thalamic nucleus reuniens mediates the transition from reactive to proactive defensive behavior via feedforward inhibition (1R03MH128654-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10354461. Licensed CC0.

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