# Defining the functional organization of cerebellar output circuits that control feeding behavior

> **NIH NIH R01** · SCINTILLON INSTITUTE FOR PHOTOBIOLOGY · 2021 · $579,227

## Abstract

Project Summary
In addition to motor and classical conditioning functions, the cerebellum contributes to motivation and reward
processes that underlie complex behaviors. To influence non-motor processes, such as feeding and food-
seeking behaviors, it is thought that the cerebellum modulates cortical and subcortical feeding centers. The only
path through which the cerebellum can influence feeding control is through cerebellar output circuits in the deep
cerebellar nuclei (DCN). Yet little is known about how DCN circuits are organized and whether distinct pathways
are dedicated to feeding and food-seeking behaviors. The recent identification of discrete subsets of DCN
neurons that project to thalamic, subthalamic and hypothalamic brain regions indicates the existence of neural
subtype organization to cerebellar output. Based on published and preliminary data, the primary hypotheses of
this proposal are that: 1) distinct DCN-mediated pathways project to known feeding centers to influence food
intake; and 2) these features identify distinct DCN circuits essential for feeding and/or metabolism; and finally,
3) dedicated DCN-mediated pathways are engaged during feeding, and influence the neural activity of specific
neuronal subtypes in key feeding centers. This proposal will test these hypotheses through three aims. Aim 1
delineates distinctions in target selectivity of specific DCN circuits. We will employ conditional viral tracing, and
genetic fate-mapping methods to define the output connectivity of DCN subpopulations to feeding centers
(paraventricular nucleus, lateral hypothalamus, arcuate nucleus and zona incerta), which we hypothesize
influence feeding behavior. Additionally, we will determine if major subclasses of arcuate neurons (e.g. POMC
or AgRP) are linked to the DCN with specific Cre-lines and trans-synaptic rabies virus. In Aim 2, we will define
the role of DCN circuits in feeding control through optogenetic activation and silencing of discrete neuronal
subpopulations in the DCN. Specifically, we will examine how selective neural manipulation of anatomically-
defined DCN pathways influences food intake and metabolism, and dissociate output pathways for motor control.
Finally, the experiments in Aim 3 will determine the activity profile of discrete DCN neuronal subpopulations, and
how activity in these subpopulations changes neural activity of known feeding circuits in freely moving mice
during food intake using deep-brain imaging. By defining the anatomical and functional organization of cerebellar
output pathways, and their activity dynamics involved in feeding behavior, these aims provide insight into more
general mechanisms of how cerebellum controls motivation and reward circuits, and establish a framework for
exploring the more enigmatic cognitive roles of the cerebellum. A more comprehensive understanding of
cerebellar function will provide greater insight into how neurological disorders and injuries disrupt food intake,
and lay t...

## Key facts

- **NIH application ID:** 10122397
- **Project number:** 1R01DK124801-01A1
- **Recipient organization:** SCINTILLON INSTITUTE FOR PHOTOBIOLOGY
- **Principal Investigator:** John Nicholas Betley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $579,227
- **Award type:** 1
- **Project period:** 2021-02-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10122397

## Citation

> US National Institutes of Health, RePORTER application 10122397, Defining the functional organization of cerebellar output circuits that control feeding behavior (1R01DK124801-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10122397. Licensed CC0.

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