# A Bioengineering Approach to Develop a Laminar 3D Cerebellar Neuronal Circuit for Modeling Human Cerebellum

> **NIH NIH R01** · SEATTLE CHILDREN'S HOSPITAL · 2022 · $634,977

## Abstract

PROJECT SUMMARY/ ABSTRACT
The formation of neuronal laminae is a fundamental feature of cortical regions of the mammalian brain. This
proposal aims to generate a defined 3D system of human cerebellar neurons that faithfully reproduces the native
lamination of the cerebellar cortex. The cerebellum is a key area to study, as an archetypal cortical structure and
as a brain region that functions both in sensory-motor control and in non-motor functions, including cognition,
emotion and language. We will use two protocols in place in the Hatten Lab to differentiate the two primary
classes of cerebellar neurons from human pluripotent stem cells (hPSCs) and state of the art bioengineering
methods to develop a defined 3D laminar culture system (Aim 1). We will then use calcium imaging of cell-type
specific genetically encoded calcium sensors to determine correlations in neuronal firing rates as a first step
toward recording circuit properties of human cerebellar neurons in a 3D in vitro laminated system (Aim 2) and
transcriptomic profiling against native developing tissue (Aim 3). Among cerebellar interneurons, unipolar brush
cells are important modulators of the cerebellar circuit, yet no protocols are available to derive them in vitro. We
will develop the first differentiation protocols to derive these glutamatergic neurons and incorporate them into
laminar models (Aim 4). This research will combine the expertise of the Millen Lab in human cerebellar
development with that of the Hatten Lab in generating human cerebellar neurons from hPSCs to provide the first
properly stratified human cerebellar circuit for the purposes of disease modeling and drug screening.

## Key facts

- **NIH application ID:** 10444198
- **Project number:** 1R01NS122902-01A1
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Mary Elizabeth Hatten
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $634,977
- **Award type:** 1
- **Project period:** 2022-04-15 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10444198

## Citation

> US National Institutes of Health, RePORTER application 10444198, A Bioengineering Approach to Develop a Laminar 3D Cerebellar Neuronal Circuit for Modeling Human Cerebellum (1R01NS122902-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10444198. Licensed CC0.

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