# Regulation of instructive signaling in the cerebellum

> **NIH NIH R01** · MAX PLANCK FLORIDA CORPORATION · 2020 · $207,741

## Abstract

Project Summary/Abstract
My long-term goal is to understand how neural circuits in the cerebellum ensure accurate movement through the
acquisition of motor learning. When cued by performance errors, climbing fiber excitation triggers a response in
postsynaptic Purkinje cells that involves both a complex spike in their somata and calcium spikes in their
dendrites. While climbing fibers are highly reliable at driving complex spikes in Purkinje cells, they are not always
effective at inducing learning. This indicates that there are specific processes during behavior that regulate the
conversion of climbing fiber activity into adaptive information for the circuit. By regulating climbing fiber-mediated
learning, inappropriate motor associations may be rejected and/or allow for other instructive signals to engage
mechanistically-distinct types of plasticity. Ultimately, these mechanisms could underlie a range of adaptive
responses that vary in time, amplitude, and direction. In this proposal, we explore the possible role of molecular
layer interneurons (MLIs) in regulating Purkinje cell excitation in response to climbing fiber activation, with special
focus on dendritic Ca2+ spikes that are particularly relevant to known mechanisms of plasticity at coactive parallel
fiber synapses. We will use quantitative measurements afforded by ex-vivo brain slice preparations to
mechanistically dissect the interplay of climbing fiber excitation and ML inhibition at Purkinje cell dendrites, and
the influence of these interactions on the climbing fiber’s ability to generate synaptic plasticity. In conjunction,
we will use in vivo methods to measure and manipulate neural activity during the acquisition of adaptive motor
responses in vestibulo-ocular system to gauge how learning is affected by MLI inhibition. Our study intersects
cellular and systems approaches to link the cell-level signaling mechanisms to synaptic plasticity and the circuit
processes that encode adaptive behavior. Because cerebellar pathology may manifest as inappropriate learning
rather than the inability to learn, completion of these aims will provide novel insight into the development of new
therapies to treat cerebellar disorders that affect motor control.

## Key facts

- **NIH application ID:** 9977802
- **Project number:** 5R01NS105958-03
- **Recipient organization:** MAX PLANCK FLORIDA CORPORATION
- **Principal Investigator:** Jason M Christie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $207,741
- **Award type:** 5
- **Project period:** 2018-09-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977802

## Citation

> US National Institutes of Health, RePORTER application 9977802, Regulation of instructive signaling in the cerebellum (5R01NS105958-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9977802. Licensed CC0.

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