# Neural circuitry mechanisms regulating adult hippocampal neurogenesis

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $380,000

## Abstract

Project Summary
 Adult hippocampal neurogenesis recapitulates the entire process of neurodevelopment in a specialized
neurogenic niche within the mature dentate gyrus (DG). The proper maturation and integration of these adult-
born neurons are crucial for cognitive functions and mood regulation. Thus, dysregulation of adult-born
neurons by developmentally-expressed genes, such as DISC1 (Disrupted-in-schizophrenia 1), leads to
cognitive and affective behavioral deficits. The DG neurogenic niche consists of multiple cell populations
including a diverse group of local interneurons with distinctive electrophysiological, molecular, and innervation
properties. However, the specific neural circuits that regulate various developmental processes of the newborn
neurons are unknown, yet such knowledge is needed to guide rational therapeutic strategies to treat disorders
arising from dysregulated adult hippocampal neurogenesis. Using optogenetic and electrophysiological
approaches, we recently identified two genetically distinct local interneuron inputs onto immature neurons:
perisomatic-targeting parvalbumin (PV) and axo-dendritic targeting somatostatin (SOM) expressing
interneurons. How distinct local interneurons and their circuitry connections encode and regulate various
developmental processes of newborn neurons during adult hippocampal neurogenesis is unknown. We
hypothesize that genetically distinct interneuron circuits regulate discrete developmental processes of newborn
neurons. Interestingly, we found that newborn neurons with DISC1 deficiency receive aberrant local
interneuron inputs from PV and SOM neurons. Furthermore, we found that dendritic and spine development of
newborn neurons with DISC1 deficiency were differentially regulated by local PV and SOM interneuron
activities. Together, these data suggested that genetic dysregulation of DISC1 may drive aberrant
development of newborn neurons in an interneuron circuit-specific fashion. We therefore hypothesize that
manipulating activities of distinct local interneurons and their circuitry connections will exacerbate or normalize
specific aspects of aberrant development in newborn neurons with DISC1 deficiency. Our results will reveal the
role of distinct neural circuits for encoding specific aspects of normal and aberrant neurodevelopment, and
guide treatment strategies targeting adult hippocampal neurogenesis.

## Key facts

- **NIH application ID:** 9983154
- **Project number:** 5R01MH111773-05
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Juan Song
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $380,000
- **Award type:** 5
- **Project period:** 2016-09-26 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983154

## Citation

> US National Institutes of Health, RePORTER application 9983154, Neural circuitry mechanisms regulating adult hippocampal neurogenesis (5R01MH111773-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9983154. Licensed CC0.

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