# Appetitive and aversive state interactions in the central amygdala during learning and memory

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $548,966

## Abstract

Project Summary
The exact nature of how positive and negative affective stimuli reciprocally interact within the brain to influence
learning and memory is not well resolved. Understanding how positive affective states impact discriminatory
threat learning, memory retention, and extinction has broad implications for the effectiveness of cognitive
behavioral therapies. Based on its connectivity to brain regions involved in threat responding, threat
generalization, the negative affect of pain, and salience detection, we hypothesize that the central nucleus of
the amygdala (CeA) is a key site for the integration positive and negative affective state information that is
important for the regulation of threat learning and the influences of affective state. Our preliminary results
demonstrate that co-presentation of a conditioned stimulus associated with positive valence with a conditioned
stimulus associated with a negative valence can prevent, reverse, or facilitate the extinction of a generalized
threat memory. We further show that this effect is dependent on the activation of neurons in the ventral
tegmental area and the modification of fear encoding neurons of the CeA by dopamine release. In this
proposal, we seek to resolve how positive stimuli influence fear encoding and threat discrimination at the level
of activation of specific neurotransmitter receptors in the CeA to facilitate discriminatory threat memories. We
further seek to resolve how positive and negative affective stimuli are differentially encoded in the CeA and
how these cell types can influence each other’s activity during positive and negative valence learning.
Resolving the basic brain mechanisms that allow positive affective stimuli to influence threat memories has
important implications for improving cognitive behavioral therapies in the treatment of generalized anxiety
disorders.

## Key facts

- **NIH application ID:** 10822032
- **Project number:** 1R01MH135538-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** LARRY S ZWEIFEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $548,966
- **Award type:** 1
- **Project period:** 2023-12-25 → 2028-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10822032

## Citation

> US National Institutes of Health, RePORTER application 10822032, Appetitive and aversive state interactions in the central amygdala during learning and memory (1R01MH135538-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10822032. Licensed CC0.

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