# A novel output pathway from the cerebellum for regulation of diverse non-motor behaviors

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2022 · $565,567

## Abstract

Abstract/Summary
In addition to its well-established role in motor function and motor learning, the cerebellum is implicated in a
myriad of non-motor behaviors. In humans, cerebellar damage can impair abstract reasoning and working
memory, and result in PTSD. In animal models, the cerebellum regulates heart rate, breathing, aggression,
appetite, fear conditioning and many other behaviors. In general, the role of the cerebellum in regulating these
behaviors is not well understood. An important step in understanding these nonmotor behaviors is to determine
the output pathway and downstream targets that allow the cerebellum to regulate these behaviors. It is known
that Purkinje cells (PCs) relay signals from the cerebellar cortex to the deep cerebellar nuclei (DCN), which in
turn activate the motor thalamus. It was assumed that DCN outputs are also responsible for nonmotor
behaviors. Here, we describe powerful and direct inhibitory connections between PCs in regions of the
cerebellum implicated in nonmotor behaviors, and neurons in the parabrachial nucleus (PBN). This is
intriguing, because the PBN contributes to many of the same nonmotor behaviors influenced by the
cerebellum. Based on our preliminary findings, we hypothesize that the PBN is a specialized cerebellar output
that allows the cerebellum to regulate nonmotor behaviors. The first step in testing this hypothesis will be to
characterize the connections between PCs and the PBN. The studies will determine the strength and
prevalence of the direct PC to PBN synapse and determine the extent to which PCs regulate the activity of
neurons in the PBN. The second major step is to identify the regions targeted by the PCPBN pathway and to
determine the contribution of this pathway to various behaviors. Preliminary studies suggest that this pathway
projects to the hypothalamus, the amygdala, and the basal forebrain, and thus has the appropriate connectivity
to allow the cerebellum to regulate diverse behaviors ranging from aggression to fear extinction. This promises
to lead to a new appreciation of the roles of the cerebellum in numerous behaviors, it will provide insight into
the circuits involved in these behaviors and it has important implications for many neurological disorders.

## Key facts

- **NIH application ID:** 10327320
- **Project number:** 5R01MH122570-03
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** WADE G REGEHR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $565,567
- **Award type:** 5
- **Project period:** 2020-03-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10327320

## Citation

> US National Institutes of Health, RePORTER application 10327320, A novel output pathway from the cerebellum for regulation of diverse non-motor behaviors (5R01MH122570-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10327320. Licensed CC0.

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