# ROLE OF CEREBELLAR CORTEX INTERNEURONS IN CEREBELLAR CORTEX FUNCTION

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $324,063

## Abstract

ABSTRACT
 The granular layer is the input layer of the cerebellar cortex. It receives information from many brain
areas through mossy fibers. It outputs information through granule cell axons to the molecular layer,
where they contact other interneurons and Purkinje cells (PCs) [1-3]. Our deep understanding of the
anatomy and physiology of the granular layer of the cerebellar cortex has made this structure an ideal
model system to study signal processing by local networks. An important consideration when studying
granular layer function is that there are different neurochemical phenotypes of granular layer
interneurons within a single morphological phenotype of interneuron [4-9]. For instance, unipolar brush
cells (UBCs) and Golgi cells can be divided into neurochemical subtypes based on the level of GABA-
A, glycine and metabotropic glutamate receptors (mGluRs) [5-7]. This neurochemical diversity is not
inconsequential, but it provides each neurochemical subtype with different functional roles. However,
little is known about the response of different morphological and neurochemical types of granular layer
interneurons in the awake behaving animal. This information is essential for a mechanistic
understanding of cerebellar cortex function. Our project is designed to provide this information.
 Our goal is to begin answering the following questions: What are the computations performed by
different classes granular layer interneurons in awake animals? How do these computations help
generate PC responses and the behavior? Our experiments will tackle these questions head on. Our
model system is the macaque ventral paraflocculus (VPFL), which is a cerebellar structure involved in
oculomotor control [10, 11]. We will use single unit recordings, pharmacology, and behavioral
measurements. In AIM 1, we will identify different morphological and neurochemical classes of granular
layer interneurons and study their response to oculomotor tasks. In AIM 2, we will quantify the effect of
pharmacological disrupting granular layer processing on the response of PCs (the sole output of the
cerebellar cortex, AIM 2A). We will also quantify the effect of pharmacological disrupting granular layer
processing on oculomotor behavior (AIM 2B). Lastly, in AIM 3, we will use the above experimental
techniques to test the hypothesis that the VPFL, and more specifically its granular layer, participates in
building an internal representation of the eye movement (i.e., a forward model of the eye movement)
[12-16]. Our preliminary data suggest that the granular layer of the cerebellar cortex performs spatial and
temporal signal transformations necessary for normal motor behavior and that the cerebellar cortex
participates in the construction of a forward model of the movement. The experimental approach and
preliminary data attest to the tremendous potential of the proposed studies to mechanistically
understand granular layer function.

## Key facts

- **NIH application ID:** 9947916
- **Project number:** 5R01DC016231-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Pablo M. Blazquez Gamez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $324,063
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9947916

## Citation

> US National Institutes of Health, RePORTER application 9947916, ROLE OF CEREBELLAR CORTEX INTERNEURONS IN CEREBELLAR CORTEX FUNCTION (5R01DC016231-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9947916. Licensed CC0.

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