# Circuits underlying threat and safety

> **NIH NIH UF1** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $4,718,512

## Abstract

Classical conditioning has been studied in many different animal models, and even in humans. However, the
larval zebrafish with its transparent brain offers a unique opportunity to observe large scale changes in
synaptic structure that accompany this form of learning. Accordingly, we have developed a novel paradigm for
visualizing synaptic changes that occur during classical conditioning in larval zebrafish. Using this paradigm we
have observed striking region-specific changes in the distributions of synapses that drive the rewiring of neural
circuits that mediate threat responses. In this grant we will expand this paradigm by monitoring neuronal
activity through imaging of genetically encoded calcium indicators throughout the pallium (the homolog of the
amygdala) before, during and after classical conditioning and extinction. This will allow us to identify cells that
comprise the circuits that control threat and safety and explore their connectivity using optogenetics. We will
investigate how different sensory inputs can cause changes in the activity of those cells leading to synapse
change, and the formation or extinction of associative memories. A crucial component of these studies will be
the recording of field potentials to capture rhythmic activity throughout the pallium and high speed SPIM
imaging of genetically encoded voltage indicators to record rhythms in individual cells. By understanding the
precise timing of signals that impinge on individual cells we will uncover mechanisms that underlie synaptic
plasticity. Our goal is to develop a theoretical model describing the neural circuits that underlie threat detection
and how they can change as a result of associative memory formation and extinction.

## Key facts

- **NIH application ID:** 10218722
- **Project number:** 1UF1NS122082-01
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** DONALD B ARNOLD
- **Activity code:** UF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $4,718,512
- **Award type:** 1
- **Project period:** 2021-04-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10218722

## Citation

> US National Institutes of Health, RePORTER application 10218722, Circuits underlying threat and safety (1UF1NS122082-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10218722. Licensed CC0.

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