# Functional roles of inhibitory cerebellar outputs

> **NIH NIH R37** · UNIVERSITY OF COLORADO DENVER · 2024 · $503,439

## Abstract

Project Summary/Abstract:
The precision and accuracy of vertebrate movement is mediated by the cerebellum. Cerebellar damage results
in a signature motor phenotype called dysmetria, characterized by prominent endpoint errors in movements
such as reaches. These endpoint deficits have been attributed to the absence of anticipatory braking signals
from the cerebellar interposed nucleus that accurately slow the limb to target. Our previous work in mice has
shown a causal role for activity in the interposed nucleus that scales the rate of reach deceleration relative to
peak reach velocity, producing stable endpoints despite reach-by-reach kinematic variability. We hypothesize
that this activity is learned and under adaptive control from Purkinje neurons and the inferior olive (IO):
Reaches that end off target will alter the frequency of teaching signals from the IO, reweight contextual signals
to Purkinje cells, and recalibrate interposed deceleration signals such that future reaching attempts land on
target. Despite this developing framework, the interposed nucleus houses multiple projection neuron types,
including inhibitory neurons that project densely to the IO, termed nucleoolivary neurons (NO). This proposal
uses our unique behavioral paradigm of closed-loop circuit manipulations to advance the cerebellar learning
hypothesis by asking how the cerebellum tunes its own teaching signals via this inhibitory output pathway and
actuates control with these neurons. Together these projections raise the intriguing possibility that the
cerebellum teaches its teachers. The outcomes of these studies will advance our long-term goal of
understanding the circuit mechanisms of feedforward motor control in mammals, which is critical for precise
movement and hypothesized to be impaired in movement disorders that involve the cerebellum.

## Key facts

- **NIH application ID:** 10990180
- **Project number:** 1R37NS131839-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Abigail L Person
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $503,439
- **Award type:** 1
- **Project period:** 2024-09-04 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10990180

## Citation

> US National Institutes of Health, RePORTER application 10990180, Functional roles of inhibitory cerebellar outputs (1R37NS131839-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10990180. Licensed CC0.

---

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