# Regulation and functional contribution of hypothalamic modified adult hippocampal neurogenesis

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $747,199

## Abstract

Project Summary
 The hippocampus has considerable importance for memory and emotion, and it is a major site of
pathophysiology associated with various neurological and psychiatric disorders. One striking feature of this brain
region is its unique capacity for adult neurogenesis, a process by which new neurons are continuously generated
from radial neural stem cells (rNSCs) throughout life in the dentate gyrus (DG). These adult-born neurons (ABNs)
undergo a critical period of heightened synaptic plasticity, during which they make unique contribution to
hippocampus-dependent behavior. Adult hippocampal neurogenesis (AHN) is dynamically regulated by neural
circuit activity. However, a long-standing question remains on whether manipulating neural circuits can induce
sufficient neurogenic effects for behavioral modulation. Recently, we identified a key subcortical region in the
hypothalamus, supramammillary nucleus (SuM), which upon activation effectively promote AHN. Specifically,
patterned stimulation of SuM neurons promotes self-renewal and neurogenic proliferation of rNSCs and
maturation of ABNs, which collectively contributes to increased production of ABNs with improved properties.
Importantly, chemogenetic manipulation of the activity of these SuM-enhanced ABNs bidirectionally modulates
memory performance and innate anxiety. These results highlight activity-dependent contribution of SuM-
enhanced ABNs in hippocampal function. Interestingly, SuM neurons are highly responsive to environmental
novelty (EN) and are required for EN-induced enhancement of neurogenesis. Building upon these findings, we
propose the following aims to decipher mechanisms underlying SuM-mediated modulation of AHN and activity-
dependent contribution of SuM-enhanced ABNs to brain-wide network dynamics. Aim 1 will determine the
contribution of SuM glutamate or GABA transmission in mediating SuM-activity or environmental-novelty induced
enhancement of hippocampal neurogenesis. Aim 2 will determine the functional properties of SuM-enhanced
ABNs and molecular regulators underlying SuM-mediated enhancement of neurogenesis. Aim 3 will determine
activity-dependent contribution of SuM-enhanced ABNs to local hippocampal circuit and brain-wide network
dynamics.

## Key facts

- **NIH application ID:** 10883640
- **Project number:** 5R01MH132222-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Juan Song
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $747,199
- **Award type:** 5
- **Project period:** 2023-07-06 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10883640

## Citation

> US National Institutes of Health, RePORTER application 10883640, Regulation and functional contribution of hypothalamic modified adult hippocampal neurogenesis (5R01MH132222-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10883640. Licensed CC0.

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