# Investigating the cerebellar circuit substrate for modulating ASD core diagnostic behaviors

> **NIH NIH F31** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $26,883

## Abstract

Project Summary
The cerebellum has repeatedly been shown to play a role in non-motor behaviors including complex cognitive
and social behaviors. Interestingly, cerebellar dysfunction has similarly been implicated in autism spectrum
disorders (ASDs) and autism-related behaviors including social interaction deficits, cognitive inflexibility and
repetitive behaviors. Human studies have also shown that cerebellar Purkinje Cell loss is one of the most
consistent postmortem findings in ASD subjects, and cerebellar injury greatly increases the risk of a later
diagnosis of ASD. Although these facts clearly implicate the cerebellum in autism-related behaviors, the role of
circuits emanating from the cerebellum to the cerebral cortex remains unknown. Our preliminary data implicate
the medial prefrontal cortex (mPFC) as a potential downstream target of the cerebellum, and we hypothesize
that ASD-related behaviors are regulated by cerebellar circuits to the mPFC via either VTA or thalamus.
We further hypothesize that we can rescue ASD-related behaviors in two mouse models of ASD by
selectively manipulating the activity of these circuits. To test this hypothesis, we propose the following
specific aims:
 Aim 1: Determine functional connectivity between the cerebellum and the mPFC. We will determine functional
connectivity by performing in vivo anesthetized single unit recordings in the left prelimbic mPFC while silencing
select Purkinje Cell activity in the cerebellum with chemogenetics.
Aim 2: Define which cerebellar-mPFC circuits mediate ASD related behaviors. Anatomical connections
between the cerebellum and the mPFC have been shown via the thalamus and Ventral Tegmental Area (VTA).
We will optogenetically inhibit the activity of these circuits in wild type mice during behavioral assays to induce
ASD relevant phenotypes to determine these circuits are necessary for these behaviors.
Aim 3: Rescue behavioral deficits in mouse models of ASD through modulation of cerebellar-mPFC circuit
activity. Behavioral assays will be conducted in mouse models of Tuberous Sclerosis as well as Fragile X
Syndrome while optogenetically manipulating cerebellar circuits via the Thalamus or VTA to the mPFC.

## Key facts

- **NIH application ID:** 9831053
- **Project number:** 5F31NS107004-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Elyza Kelly
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $26,883
- **Award type:** 5
- **Project period:** 2018-12-01 → 2020-06-26

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9831053

## Citation

> US National Institutes of Health, RePORTER application 9831053, Investigating the cerebellar circuit substrate for modulating ASD core diagnostic behaviors (5F31NS107004-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9831053. Licensed CC0.

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