# Cerebellar Modulation of Innate Defensive Behaviors

> **NIH NIH R00** · COLORADO STATE UNIVERSITY · 2023 · $249,000

## Abstract

Innate defensive behaviors promote survival by allowing animals to detect and respond to threats within their environment, such as predators. Although innate, these defensive behaviors show a remarkable amount of flexibility and are subject to robust habituation, suggesting that the circuitry underlying defensive behaviors is subject to modulatory control. Our recent work suggests that the cerebellum may provide one source of afferent modulatory influence within the periaqueductal gray. We find that cerebellar afferents to the freezing-related circuitry in ventrolateral periaqueductal gray (vlPAG) predominantly activate local dopaminergic interneurons, which subsequently alter the relative strength of synaptically evoked inhibition and excitation onto freezing premotor neurons. More specifically, cerebellar activation increases IPSC amplitudes and decreases EPSC amplitudes, which is predicted to increase spike threshold and alter the input-output relationship, altering the integrative properties of freezing premotor neurons. These results motivate testing the hypothesis that the cerebellum modulates the expression of innate defensive behaviors through activation of local vlPAG dopamine neurons. To test this hypothesis, a combination of in vivo behavioral and systems-level approaches will be used to manipulate cerebellar input and record cerebellar activity during innate freezing behaviors to determine the nature of the cerebellar signals produced, and their resulting effects on expression of freezing behavior. To study the role of vlPAG dopamine neurons in modulating innate freezing behaviors, I will similarly record and manipulate vlPAG dopamine neuron activity using fiber photometry and optogenetic actuators. Finally, because selective lesions of vlPAG dopamine neurons disrupt both fear memory formation in mice (as do disruptions in cerebellar plasticity), I will test the hypothesis that cerebellar associative plasticity contributes to fear memory formation by modulating vlPAG dopamine activity. Together, these experiments provide a framework for understanding how the cerebellum modulates both innate freezing and more broadly how cerebellar plasticity contributes to learned defensive behaviors.

## Key facts

- **NIH application ID:** 10703716
- **Project number:** 4R00NS119783-03
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Christopher Edward Vaaga
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10703716

## Citation

> US National Institutes of Health, RePORTER application 10703716, Cerebellar Modulation of Innate Defensive Behaviors (4R00NS119783-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10703716. Licensed CC0.

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