# Project 1: The Origin and Diversity of Human GABAergic Interneurons

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $266,473

## Abstract

PROJECT SUMMARY
Cortical interneurons are a diverse set of local inhibitory cells essential for proper balance of
excitation and inhibition and key to brain function. Abnormal development of interneurons can
lead to severe neuropsychiatric disorders (interneuropathies). Identification of the molecular
pathways and cellular populations implicated in these disorders is necessary to understand their
etiology and to improve our ability to predict which individuals are at risk. Work from our original
grant demonstrated that the infant frontal lobe maintains a large population of migratory
interneurons for several months after birth. This collection of migrating young neurons (Arc)
targets many areas of the infant frontal lobe. These cells contribute importantly to the final
interneuron composition of the human brain (e.g. cingulate gyrus). The human cortex,
therefore, continues to receive interneurons for several months after birth, especially in areas of
higher cognition implicated in neurodevelopmental disorders. Similarly, our recent evidence
shows that the human amygdala continues to receive many young neurons postnatally. These
observations significantly change how we view the development of the infant brain and raise the
need to better understand the origins of human cortical interneurons, including those that
migrate postnatally in the Arc. Young neurons in the human Arc and amygdala are postmitotic
(Ki67-), supporting the hypothesis that they are not generated within these regions. The
expression pattern of regional transcription factors in the Arc, suggests that they come from the
developing human ventral forebrain; the Medial and Caudal Ganglionic Eminences (hMGE and
hCGE). The project's overall goal is to understand how the human GE generates large
numbers and diverse types of cortical interneurons by studying its development during the mid-
late gestation and early postnatal life. We will determine the genetic and molecular properties of
proliferative populations in the hMGE, hLGE, and hCGE using human postmortem brain
samples from neonatal and infant cases (up to 6 months after birth), define how interneuron
subtypes arise in the perinatal human brain. The proposed studies will identify the unique and
sustained properties of human inhibitory neuron development. By using a multi-disciplinary
approach (including transcriptomic, histological, and acute slice cultures), we aim to establish
how interneurons are made in the human brain and provide the fundamental knowledge needed
to understand their role in disease.

## Key facts

- **NIH application ID:** 10408733
- **Project number:** 5P01NS083513-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Arturo Alvarez-Buylla
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $266,473
- **Award type:** 5
- **Project period:** 2014-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10408733

## Citation

> US National Institutes of Health, RePORTER application 10408733, Project 1: The Origin and Diversity of Human GABAergic Interneurons (5P01NS083513-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10408733. Licensed CC0.

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