# The interactive roles of the amygdala and orbitofrontal cortex during reversal learning

> **NIH NIH R21** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $202,500

## Abstract

As animals move about in the environment, they must be able to rapidly assess and
update the meaning of cues around them in order to approach reward and avoid danger.
Reversal learning, a paradigm commonly used to test behavioral flexibility, involves
switching the association between a stimulus and its outcome. For example, a tone that
initially predicted a sweet tastant can come to predict a bitter tastant. Two brain regions,
the orbitofrontal cortex (OFC) and basolateral amygdala (BLA), are involved in tasks that
demand flexible responses to the changing significance of stimuli during reversal
learning. While several studies have provided evidence that the OFC and BLA interact
during reversal learning, little is known about the specific mechanisms of this interaction.
In this grant, we propose to use a combination of genetic and cellular imaging
techniques in mice to identify and characterize the physiological response properties
during reversal learning of BLA neurons that project to OFC. The reversal learning task
we employ involves stimuli of multiple modalities that predict outcomes of both positive
and negative value to thoroughly elucidate the differential response properties of BLA
neurons to stimuli that change their associated reinforcement outcome (Aim 1). In these
experiments, the physiological response properties of neurons identified as projecting
from BLA to OFC will be compared to the response properties of the overall population.
Then, using an optogenetic approach, we will test the causal role of OFC input onto BLA
neurons during reversal learning by inhibiting the specific projections from OFC to BLA
to test their causal role on behavioral flexibility and on the nature of representations in
BLA (Aim 2). The data analysis for both aims involves collaboration with theoretical
neuroscientists to use linear classifiers and other sophisticated techniques to understand
the nature and dynamics of neural encoding in BLA and its relation to behavior. These
experiments promise to shed light on the mechanisms by which cortico-amygdalar
circuits mediate flexibility critical for adaptive emotional responses and behavior, an
ability that is impaired in individuals with psychiatric disorders.

## Key facts

- **NIH application ID:** 9842566
- **Project number:** 5R21MH116348-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** C. DANIEL SALZMAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $202,500
- **Award type:** 5
- **Project period:** 2018-12-24 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842566

## Citation

> US National Institutes of Health, RePORTER application 9842566, The interactive roles of the amygdala and orbitofrontal cortex during reversal learning (5R21MH116348-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9842566. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*