# Neural Circuit Control of Postnatal Quiescent Neural Stem Cell Activation

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $534,283

## Abstract

ABSTRACT
It has become increasingly clear that systemic signals and external stimuli can alter neurodevelopmental
programs, and that early developmental defects become significant contributors to behavioral sequelae
later in life. Despite our current understanding of neurogenesis control, it remains largely unclear what
functions neural circuit activity patterns may exert on NSC proliferation and differentiation during
development. The rodent postnatal lateral ventricular (LV) germinal matrix/neurogenic niche is a
specialized environment housing GFAP+ astrocytes functioning as NSCs, producing mainly GABAergic
interneurons. It is analogous to the postnatal human LV germinal matrix, where robust neurogenesis
persists for up to two years after birth. The postnatal LV niche serves as an excellent model system to
study molecular mechanisms regulating neurogenesis, both in health and in disease states. Postnatal LV
neurogenesis is regulated by NSC-intrinsic mechanisms, interacting with extracellular/niche-driven cues.
It has been generally accepted that these local effects are responsible for sustaining neurogenesis,
though behavioral paradigms and disease states have suggested possibilities for neural circuit-level
modulations. It is currently unclear if activity patterns from groups of neurons, or discrete neural circuits,
can respond to external stimuli and control NSC proliferation in the postnatal brain. We have identified
long-range neuronal projections that can provide excitatory drive to local neurons within the postnatal LV
niche. Our preliminary results have uncovered putative downstream targets of this previously
undescribed neural circuit, the quiescent NSCs, suggesting an exciting connection between external
inputs and NSC activation. We plan to further explore these observations by determining the following: 1)
the cellular identity of the postnatal LV quiescent NSCs; 2) which brain regions can serve as a relay for
external stimuli to induce LV NSC proliferation; and 3) which postnatal radial glial progenitors, and their
activity-dependent maturation process, are responsible for constructing the neural circuits to direct
quiescent NSC activation. Our proposal explores a direct connection between neuronal activity patterns
from discrete circuits and postnatal NSC proliferation. To make this research question tractable, we have
developed new mouse reagents, as well as experimental platforms to measure the interactions between
patterns of neuronal activity and NSC proliferation. We believe findings from these experiments will
significantly advance our understanding of how neural circuit activity controls stem cell proliferation in the
postnatal brain in health and disease.

## Key facts

- **NIH application ID:** 10072307
- **Project number:** 2R01MH105416-06
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Henry Yin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $534,283
- **Award type:** 2
- **Project period:** 2014-11-19 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072307

## Citation

> US National Institutes of Health, RePORTER application 10072307, Neural Circuit Control of Postnatal Quiescent Neural Stem Cell Activation (2R01MH105416-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10072307. Licensed CC0.

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