# Neural mechanisms of active avoidance behavior

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2021 · $555,357

## Abstract

Summary
 Enormous progress has been made about the neural substrates of Pavlovian fear conditioning. In this
paradigm, the association between an initially neutral sensory stimulus with an aversive event (footshock)
leads to the transformation of the neutral stimulus into a conditioned stimulus (CS) that elicits fear responses in
the form of immobility, potentiated startle, changes in heart rate, etc, which were not evoked by the neutral
sensory stimulus. Ample evidence indicates that the CS must be transmitted through the modality-specific
sensory thalamus to reach emotional processing centers in the amygdala, where the association with the
aversive stimulus occurs and an output drives the conditioned responses. In contrast, little is known about the
neural circuits involved in active avoidance behavior. In this paradigm, subjects learn to avoid an aversive
event by producing an appropriate behavioral response (avoidance) during an interval signaled by the
presentation of a CS. Understanding active avoidance behavior is important because it is present in most
forms of pathological anxiety. Using optogenetics and chemogenetics, we recently found that the output of the
basal ganglia through GABAergic neurons in the substantia nigra pars reticulata (SNr) fully controls active
avoidance. SNr excitation blocks active avoidance without interfering with the ability to escape the harmful
event, while SNr inhibition facilitates avoidance or can drive it in the absence of an external CS. With this work
as a backdrop, we have developed a hypothetical model of the neural circuits involved in the performance
(expression) of active avoidance behavior. Here we propose to test key aspects of this model. Our hypothesis
is that SNr mediates active avoidance behavior though its projections to specific portions of the midbrain that
drive the locomotor responses needed to avoid. Moreover, specific regions of the striatum control SNr activity
during avoidance via striatonigral connections. We will employ a combination of behavioral,
electrophysiological, optogenetics, chemogenetics, pharmacological and histological procedures to test these
ideas. The long term objective of this research project is to reveal the neural substrates of active avoidance
behavior, which has direct relevance to many psychiatric disorders.

## Key facts

- **NIH application ID:** 10307216
- **Project number:** 7R01NS104810-04
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Manuel A Castro-Alamancos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $555,357
- **Award type:** 7
- **Project period:** 2020-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10307216

## Citation

> US National Institutes of Health, RePORTER application 10307216, Neural mechanisms of active avoidance behavior (7R01NS104810-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10307216. Licensed CC0.

---

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