# Circuit mechanisms of cerebellar control of reaching movements

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2023 · $322,190

## Abstract

PROJECT SUMMARY/ABSTRACT
Reaching movements are fundamental to human interactions with the environment. Cerebellar damage impairs
reach precision and accuracy, but the mechanistic contribution of cerebellum to reach control is unclear.
Recent work has illuminated principles of cerebellar feedforward control, where Purkinje cells learn predictive
contingencies, termed forward models, but our understanding of control signals issued from the cerebellar
nuclei, particularly to improve reach precision, is poor. The proposed studies leverage our discoveries made in
the previous grant cycle, identifying and characterizing internal motor copy pathways, to test mechanisms of
cerebellar predictive control. Outcomes of these studies will reconcile diverse hypotheses of cerebellar motor
control and identify circuit mechanisms by which feedforward motor control is produced. We have identified
strong endpoint-aligned neural activity in the cerebellar interposed nucleus of reaching mice and showed,
using closed-loop optogenetics that this activity exerts a causal pull on the limb, sculpting reach endpoint. In
the proposed studies we will explore this code to test its role in real-time control, learning and sequencing. In
aim 1 we will identify the cell-types that produce this activity and its role in shaping reach kinematics on a trial-
by-trial basis to improve precision. In aim 2, we explore whether reach adaptation changes neural patterns in
the cerebellar nuclei associated with endpoint control. Finally, in Aim 3 we leverage findings from the previous
grant cycle where we characterized anatomical and physiological properties of a feedback pathway from
cerebellar output neurons back to the cerebellar cortex ending as mossy fibers. We will examine the
contribution of this internal feedback pathway in reach control, testing the hypothesis that this fast feedback
regulates time-varying neural and behavioral sequencing. 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:** 10656246
- **Project number:** 5R01NS114430-05
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Abigail L Person
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $322,190
- **Award type:** 5
- **Project period:** 2019-09-18 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10656246

## Citation

> US National Institutes of Health, RePORTER application 10656246, Circuit mechanisms of cerebellar control of reaching movements (5R01NS114430-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10656246. Licensed CC0.

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