# Exploring cortical inhibitory circuit design in the human brain

> **NIH NIH DP2** · DUKE UNIVERSITY · 2024 · $1,380,070

## Abstract

PROJECT SUMMARY
A basic understanding of human neural circuit design is essential to grasping neurological disease processes
and developing targeted brain therapies. However, due to a shortfall of human experimental platforms,
scientists have investigated neural circuits in model systems that lack the constituent cell types and
organizational principles of the human brain. As a result, we are left with a poor understanding of how human
neural circuits are configured, impacted by disease processes, and targeted for therapeutic purposes. Here our
laboratory will pursue innovative research approaches that specifically advance our knowledge of human
neural circuits. Using live brain specimens collected from neurosurgical procedures and CellREADR, a novel
genetic tool for cellular access, we will investigate the cellular properties and circuit functional roles of human
cortical interneurons. Cortical interneurons are the principal inhibitory cellular elements of neural circuits in
the cerebral cortex, and their dysfunction has been implicated in various brain disorders such as epilepsy,
autism, and Alzheimer’s. While scientists have detailed interneuron form and function in laboratory mice, the
cellular diversity, circuit functions, and pathophysiologies of human interneuron populations remain almost
entirely unknown. Here, using a range of anatomical, physiological, and transcriptomics methods in ex vivo
human brain tissues, we will generate a multimodal phenotypic catalog of human interneurons and
characterize their functional organization in neural circuits. These studies will advance generalizable strategies
for human cellular and circuit neuroscience, while furthermore yielding a fundamental understanding of
human interneurons and human inhibitory circuit design.

## Key facts

- **NIH application ID:** 10910551
- **Project number:** 1DP2MH140149-01
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Derek G. Southwell
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,380,070
- **Award type:** 1
- **Project period:** 2024-09-06 → 2027-09-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10910551

## Citation

> US National Institutes of Health, RePORTER application 10910551, Exploring cortical inhibitory circuit design in the human brain (1DP2MH140149-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10910551. Licensed CC0.

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