# Developing innovative tools to investigate the anatomy and molecular profile of striatal cholinergic interneurons

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $10,568

## Abstract

Abstract
 The striatum is a subcortical brain region critical for action selection, learning, and motor behavior.
Striatal cholinergic interneurons (ChIs) are the primary source of local acetylcholine, and play an
important role in modulating striatal circuits. Consequently, ChIs are dysregulated in many
neuropsychiatric disorders that involve striatal dysfunction, such as Parkinson's disease, Alzheimer's
disease, and dystonia. Despite their importance, little is known about ChI structure and function. ChIs are
a sparse cell type, comprising only ~1% of all striatal neurons, yet have tremendous territorial influence
by sending out dense projections. The complete morphology and local network anatomy of ChIs remain
unknown. Furthermore, a recent study suggested ChIs are not homogenous as previously believed, but
may be divided into subtypes based on morphology and molecular markers. However, the correlation
between ChI anatomy and molecular profiles has yet to be elucidated.
 This proposal seeks to expand our understanding of ChI anatomy and molecular profiles by
developing new tools to answer questions that were impossible to address before. Although previously
understood to be an aspiny, homogenous population, my preliminary data demonstrates the existence of
a new ChI morphological subtype: spiny ChIs. I will characterize the complete morphologies of spiny and
aspiny ChIs by combining Brainbow with new clearing and expansion technology. I will then develop
technology to simultaneously visualize morphology and interrogate the molecular profile of ChIs in order
to correlate the two. These studies will increase our understanding of ChI cell types, and reveal
fundamental principles of how their anatomy and molecular profiles contribute to function. The novel tools
developed in this project will also be disseminated for the benefit of the neuroscience community. Finally,
completing this proposal will help drive me towards my long-term goal of becoming a physician scientist
by providing me with rigorous scientific, technical, and clinical training.

## Key facts

- **NIH application ID:** 9911988
- **Project number:** 5F31NS111847-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Fred Yonghe Shen
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $10,568
- **Award type:** 5
- **Project period:** 2019-04-01 → 2020-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9911988

## Citation

> US National Institutes of Health, RePORTER application 9911988, Developing innovative tools to investigate the anatomy and molecular profile of striatal cholinergic interneurons (5F31NS111847-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9911988. Licensed CC0.

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