# Cerebellar granule cell dysfunction in Shank3 mutant mice

> **NIH NIH R01** · SOUTHERN ILLINOIS UNIVERSITY SCH OF MED · 2024 · $376,374

## Abstract

PROJECT SUMMARY/ABSTRACT
 Autism spectrum disorder (ASD) is a complex neurological disorder associated with a broad collection of
genetic mutations and environmental factors. While identifying the neural underpinnings of ASD has been a
major focus in the field of genetics and neuroscience, it is not clear which brain region (s) and cell types may be
functioning abnormally to give rise to ASD. The cerebellum, a brain region typically considered to be involved in
motor coordination and control, has received considerable attention for its potential role in ASD, with a growing
body of clinical evidence correlating ASD diagnoses with abnormalities in cerebellar anatomy, function, and
motor or vestibular behaviors/functions. In parallel, cerebellar involvement in circuits outside of the motor system
provides a substrate for the cerebellum to influence non-motor behaviors and processes, setting the stage for
the importance of appropriate cerebellar function in a host of neural processes. Within the cerebellum, the initial
integration of all incoming sensorimotor information entering the cerebellar cortex is carried out by the
morphologically simple and extremely dense population of granule cells. These granule cells also express many
high risk ASD-linked genes, especially those involved in synaptic transmission and development. However, little
is known about the role and importance of many ASD-linked genes in the cerebellum, especially in granule cells.
It is also not clear what aspects of cerebellar granule cell function and connectivity may be important for shaping
certain non-motor (and motor) behaviors. To address this knowledge gap, in aims 1 and 2 we propose to identify
the degree to which an ASD-linked gene determines properties of cerebellar granule cell synaptic interactions
and cortical circuitry dynamics over time. In Aim 3, we will identify how a particular ASD-linked gene in cerebellar
granule cells influence behavioral phenotype across motor and non-motor domains. Results from the proposed
work will be key in identifying a mechanistic link between a gene/protein linked to ASD and specific synaptic
abnormalities in the cerebellum.

## Key facts

- **NIH application ID:** 10828450
- **Project number:** 5R01MH129749-03
- **Recipient organization:** SOUTHERN ILLINOIS UNIVERSITY SCH OF MED
- **Principal Investigator:** Ben D Richardson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $376,374
- **Award type:** 5
- **Project period:** 2022-06-23 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10828450

## Citation

> US National Institutes of Health, RePORTER application 10828450, Cerebellar granule cell dysfunction in Shank3 mutant mice (5R01MH129749-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10828450. Licensed CC0.

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