# Continuous neurogenesis in the mammalian hippocampus

> **NIH NIH R35** · UNIVERSITY OF PENNSYLVANIA · 2020 · $750,339

## Abstract

SUMMARY
Adult hippocampal neurogenesis has garnered significant interest over the past two decades as a robust and
unique form of plasticity in a region critical for learning and memory. It has also proven to be fertile ground for
understanding fundamental principles of stem cell biology, neuronal development, as well as illustrating the
capacity of the mature brain to integrate immature neurons, which has important implications for regeneration
and transplantation efforts for neural repair following injury or diseases. Despite considerable progress in
understanding the molecular and cellular mechanisms underlying adult neurogenesis, there are still critical
outstanding questions in the field that have not been addressed due to the technical limitations of traditional
experimental approaches. In the proposed series of studies, we will use several cutting-edge techniques that
we have developed or adapted to investigate the developmental origin of adult neurogenesis, its functional
impact in the adult brain, and the fidelity of rodent models to human neuronal development. First, we will
characterize the origin and properties of embryonic neural precursor cells that give rise to the largely quiescent
pool of neural stem cells that maintain neurogenesis throughout life in a rodent model. Building on our recent
findings that Hopx-expressing neural progenitors in the embryonic dentate gyrus can generate the constitutive
populations in the dentate gyrus before adopting a quiescent state indicative of adult neural stem cells, we will
identify the molecular mechanisms regulate this precursor population and its transition into quiescence. These
studies will provide novel insight into the intrinsic and extrinsic signaling cues that establish a long-term pool of
stem cells in the developing and adult brain. Second, we have developed a 3D organoid model of dentate
gyrus development using human induced pluripotent stem cells to investigate the properties of neural
progenitors, neurogenesis and fate specification. These studies could lead to the potential identification of
human-specific markers of neural stem cells and new granule neurons in the dentate gyrus and mechanistic
differences and similarities with rodent models, which would inform the current debate over the extent of
postnatal neurogenesis in the human dentate gyrus. Third, we will investigate the functional properties of adult
neurogenesis in adult behaving mice using an optogenetic strategy to identify and record electrophysiological
activity of single newborn granule cells at different stages of maturation. We will also investigate the circuit-
level impact of silencing these cells at the population level. These data would provide novel information to
evaluate the hypothesis that adult-born granule cells make a unique contribution to information processing in
the hippocampus using techniques with high temporal resolution. Together, these studies combine an array of
approaches to answer fundament...

## Key facts

- **NIH application ID:** 9986189
- **Project number:** 1R35NS116843-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** HONGJUN SONG
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $750,339
- **Award type:** 1
- **Project period:** 2020-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986189

## Citation

> US National Institutes of Health, RePORTER application 9986189, Continuous neurogenesis in the mammalian hippocampus (1R35NS116843-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9986189. Licensed CC0.

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