# Reconstruction and Regulation of Neural Circuitry by Human Neurons

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $334,688

## Abstract

ABSTRACT
Cell therapy holds promise for CNS disorders. This is suggested by clinical benefits in some Parkinson's
disease (PD) patients who received transplantation of human fetal mesencephalic tissues to replace
degenerated midbrain dopamine (mDA) neurons. The ability to produce functional neurons efficiently from
human pluripotent stem cells (PSCs) expands the prospect of cell therapy. However, cell therapy for many
neurological conditions faces major hurdles. In particular, transplanted neurons often fail to reconstruct a
functional circuit that is specific to lost function. In PD, DA neurons are often transplanted directly into the
striatum, rather than their home location substantial nigra. Consequently, the grafted cells and their
repaired circuit lose appropriate inputs for functional modulation.
To address these critical issues, we will reconstruct the nigra-striatal circuit by cell transplantation to the
nigra in a PD model mouse and determine if the grafted human mDA neurons project specifically to the
striatum to form functional circuit and if the reconnection is sped up by regulating graft activity (Aim 1).
Furthermore, we will explore to regulate the neural circuit repaired by transplanted cells by expressing
active or inhibitory form of DREADD (designer receptor exclusively activated by designer drug) in hPSCs
so that the therapeutic outcomes may be refined (Aim 2). Information gained from this study will be
instrumental for restoring and regulating neural circuitry in PD and other neurological conditions.

## Key facts

- **NIH application ID:** 9828650
- **Project number:** 5R01NS096282-04
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Su-Chun Zhang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $334,688
- **Award type:** 5
- **Project period:** 2016-12-15 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828650

## Citation

> US National Institutes of Health, RePORTER application 9828650, Reconstruction and Regulation of Neural Circuitry by Human Neurons (5R01NS096282-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9828650. Licensed CC0.

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