# Circuit mechanisms of cerebellar control of reaching movements

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2024 · $503,754

## Abstract

PROJECT SUMMARY/ABSTRACT
The precision and accuracy of vertebrate movement is mediated, in part, by the cerebellum. Two primary
divisions of the cerebellum – the cortex and nuclei – are clearly delineated modules that contribute to
behaviorally-relevant computations. Sensorimotor information is first processed by the cortex and is then relayed
to the nuclei by Purkinje cells (PCs). The resultant output of the cerebellar nuclei has profound influence on
downstream motor control, motivating questions of how nuclear activity is controlled by PCs. In a model behavior,
mouse reaching, reach endpoint dysmetria, a hallmark of cerebellar damage, is attributed to the dysfunction of
anticipatory braking signals from the cerebellar interposed nucleus that slow the limb near the intended target
location. This proposal builds on observations in the previous cycle that the firing rates between Purkinje neurons
and their targets in the interposed nucleus are inverse of one another, consistent with a population rate code
mediating information transfer. However, in addition to inverse rate coding, we find, as in other species and
behaviors, that Purkinje neurons synchronize simple spike firing selectively during behavior. Our proposed
studies investigate the sufficiency of PC rate and temporal coding to generate behaviorally relevant adjustments
to reach kinematics in mice.The objective of this proposal is to testthe central hypothesis that cerebellar cortical
circuits selectively transmit population activity through a synergistic rate and temporal code, imparted by local
cortical inhibition, and that this code is refined by learning. We propose to delineate the behavioral significance
of PC population coding, how it is generated by cerebellar circuitry, and how motor learning engages the dual
nature of this synergistic rate and temporal code. RELEVANCE TO PUBLIC HEALTH: Future therapies targeted
at ameliorating cerebellar disease will increasingly leverage understanding of computational mechanisms of the
structure, thus identifying those principles, the goal of this proposal, is of central importance.

## Key facts

- **NIH application ID:** 10811961
- **Project number:** 2R01NS114430-06
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Jason M Christie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $503,754
- **Award type:** 2
- **Project period:** 2019-09-18 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10811961

## Citation

> US National Institutes of Health, RePORTER application 10811961, Circuit mechanisms of cerebellar control of reaching movements (2R01NS114430-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10811961. Licensed CC0.

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