# Unraveling the Dynamic Role of Purkinje Cell Neurotransmission in Neurodevelopment.

> **NIH NIH K08** · BAYLOR COLLEGE OF MEDICINE · 2021 · $191,108

## Abstract

Neurodevelopmental disability arising from prematurity poses a large and increasing disease burden and has
increasingly been associated with cerebellar pathogenesis. Cerebellar development coincides with a critical
developmental period during which establishment of brain networks supports neurotypical outcomes. However,
the precise role of the cerebellum in supporting network structure and function through early development is
poorly understood. Developing interventions to prevent and treat neurodevelopmental disability associated with
associated with prematurity requires a comprehensive understanding of the dynamic circuit response to
functional perturbations. This proposal uses unique features of mouse development in combination with the
sophistication of mouse genetic manipulations to dynamically alter cerebellar function through a critical
developmental window while comprehensively characterizing the resulting anatomic, physiologic, and behavioral
disruptions of the associated networks. The central hypothesis of this proposal is that cerebellar function is first
required for structural establishment of brain networks while subsequently being important for ongoing function,
a dynamic that underlies the spectrum of neurodevelopmental disability. This proposal will take advantage of a
model for inducible silencing of Purkinje cell neurotransmission developed by the candidate. In Aim 1, the
experiments will test how early vs late cerebellar disruption affects behavior, predicting that early silencing will
have pervasive behavioral deficits while late silencing will produce domain specific functional deficits. In Aim 2,
the experiments are designed to examine how early vs late silencing affects the assembly and function of brain
circuits using anatomic and electrophysiologic analyses. With these aims, the proposal outlines a rigorous
approach that combines dynamic genetic perturbations, quantitative anatomic and electrophysiologic analyses,
and cross-domain behavioral assays to better understand how early cerebellar insult contributes to
neurodevelopmental disability. The candidate is a trained pediatric neurologist with extensive clinical exposure
to diagnosis and treatment of neurodevelopmental disorders, application and analysis of basic and advanced
imaging techniques, and research experience in model organism behavioral assays. This proposal is mentored
by Dr. Roy Sillitoe, a leader in cerebellar neuroscience who has strong track record of NIH funding, mentorship,
and scientific leadership. All experiments will be conducted at the Neurologic Research Institute, a pediatric
neurology research facility that draws on the clinical excellence of Texas Children’s Hospital and the world-class
neuroscience of Baylor College of Medicine. The professional development and training plan is designed to poise
the candidate for a career as a physician scientist focused on the prevention and treatment of
neurodevelopmental disability in the pediatric populat...

## Key facts

- **NIH application ID:** 10191576
- **Project number:** 1K08NS121600-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Jason Singh Gill
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $191,108
- **Award type:** 1
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10191576

## Citation

> US National Institutes of Health, RePORTER application 10191576, Unraveling the Dynamic Role of Purkinje Cell Neurotransmission in Neurodevelopment. (1K08NS121600-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10191576. Licensed CC0.

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