# Activity dependent integration of chandelier cells during cortical circuit assembly

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $558,496

## Abstract

ABSTRACT
 Despite major progress in understanding the embryonic origin and migration of major classes of
cortical GABAergic interneurons, how distinct interneuron types are deployed to cortical layers with
appropriate density and are integrated into cortical circuits remains unexplored. The chandelier cells
(ChCs) represent a bona fide interneuron type that specifically innervates pyramidal cells (PCs) at axon
initial segment, the site of action potential initiation. Using state-of-the-art mouse genetic approaches, we
have established a robust experiment system for studying the assembly of a stereotyped ChC-PC circuit
module. We have previously discovered that ChC fate is specified from progenitors of the medial
ganglionic eminence during late neurogenesis. Once specified through lineage and birth timing
mechanisms, young ChCs appear endowed with cell-intrinsic programs that guide their migration to
achieve distinct laminar settlement. Importantly, ChCs in mature cortex mediate directional inhibitory
control between PC ensembles defined by projection targets. The developmental mechanisms to
achieve such exquisite specificity is unknown. In this proposal, we examine the general hypothesis that
activity-dependent ChC apoptosis contributes to sculpting the selective connectivity between ChCs and
PCs in the visual cortex, where we aim to link development mechanisms to functional significance.
Based on substantial evidence, our Overall Hypothesis is that ChC density and connection specificity at
the border region between primary and secondary visual cortex (V1 and lateral V2) is regulated by
contra- and ipsi-lateral callosal PC inputs (CALPC), which are coordinated by retinal activities; and
reduced innervation of CALPCs by ChCs may facilitate bilateral communication that integrates Inter-
hemispheric visual response properties. We will first characterize the development of ChC-PC
connectivity at V1/V2 border region (Aim1). We will then determine how contralateral CALPC axons and
activity regulate ChC density at the border (Aim2). We will further determine how retinal activities
regulate ChC density at V1/V2 border (Aim3). Finally, we will examine the role of ChCs in regulating
bilateral synchronization of visual response properties in the two visual hemispheres (Aim4). Our study
will provide exceptional clarity in elucidating how genetic and activity dependent mechanisms coordinate
to shape circuit wiring with cell type resolution in the mammalian brain. These studies will reveal novel
activity-dependent mechanisms of neuronal pruning that shape highly specific circuit connectivity and
may have implications in neurodevelopmental disorders such as autism spectrum disorders and
schizophrenia.

## Key facts

- **NIH application ID:** 10212920
- **Project number:** 5R01MH094705-10
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Z JOSH HUANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $558,496
- **Award type:** 5
- **Project period:** 2011-07-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212920

## Citation

> US National Institutes of Health, RePORTER application 10212920, Activity dependent integration of chandelier cells during cortical circuit assembly (5R01MH094705-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10212920. Licensed CC0.

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