# Prefrontal amygdala interactions in fear conditioning

> **NIH NIH R01** · UNIVERSITY OF PUERTO RICO MED SCIENCES · 2021 · $375,000

## Abstract

Pursuit of reward and avoidance of threat are two major behavioral motivators. Failure to balance these
motivations results in maladaptive decisions and may underlie various pathological conditions. The
sustained threat construct of the NIMH Research Domain Criteria (RDoC) includes avoidance, conflict
detection, and perseverative behaviors. Sustained threat reactions interfere with the pursuit of rewarding
activities that can decrease social interactions and trigger depression. Little is known about how decisions
guide behavior during approach-avoidance conflict. The first phase of this MERIT shifted our focus from
Pavlovian fear conditioning to active avoidance, exploring how prefrontal-amygdala-striatal circuits express
and extinguish active avoidance. For the second MERIT phase, we have developed a new task that
maximizes approach-avoidance conflict within a timed cue encounter that pits active avoidance against the
pursuit of food. The new approach-avoidance conflict task has revealed three distinct behavioral
phenotypes: 1) food-preferring rats that pursue food throughout the tone with little or no avoidance; 2)
avoidance-preferring rats which avoid throughout the tone with little or no food-seeking; and 3) timers which
seek food early in the tone and avoid later, thereby maximizing both access to food and safety. We will
capitalize on these unique behavioral phenotypes to characterize the circuits mediating approach-
avoidance decisions, using electrophysiological, immunohistochemical, and optogenetic methods. We will
use both male and female rats in all our aims. Aim 1 will use immunohistochemistry combined with
electrophysiology and fiber photometry to identify the circuits involved in conflict decision making. Aim 2 will
test the circuits identified in Aim 1 with optogenetic manipulations. Aim 3 will assess the power of this task
to identify new multi-dimensional behavioral phenotypes integrating conflict strategies with anxiety and
social interactions. This research program will enable us to characterize decision-making circuits underlying
different strategies for resolving approach-avoidance conflict.
RELEVANCE (See instructions):
Failure to balance pursuit of reward and avoidance of threat results in maladaptive decisions and
pathological conditions including anxiety and depression. Using a novel rodent task that maximizes
approach-avoidance conflict, we will characterize the circuits mediating approach-avoidance decisions
using electrophysiological, immunohistochemical, and optogenetic methods. This research program will
enable us to characterize circuits for resolving approach-avoidance conflict.

## Key facts

- **NIH application ID:** 10160651
- **Project number:** 5R01MH058883-25
- **Recipient organization:** UNIVERSITY OF PUERTO RICO MED SCIENCES
- **Principal Investigator:** Christian Emmanuell Bravo-Rivera
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $375,000
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10160651

## Citation

> US National Institutes of Health, RePORTER application 10160651, Prefrontal amygdala interactions in fear conditioning (5R01MH058883-25). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10160651. Licensed CC0.

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