# Role of hippocampal adult-born granule cells in TBI-induced dentate gyrus circuit pathology and pattern separation deficit

> **NIH NIH F31** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2020 · $39,130

## Abstract

Project Summary
Traumatic brain injury (TBI) is a highly prevalent health issue that results in cognitive and psychological deficits
such as memory dysfunction, depression, anxiety, and epilepsy. Following TBI in rodent models, there is a
robust and transient increase in hippocampal adult neurogenesis. Adult-born granule cells (abGCs) born in
response to cortical impact injury exhibit altered morphology and migration patterns, suggesting these neurons
may make aberrant connections within the dentate gyrus network. Normally, abGCs mature to form functional
excitatory synapses onto parvalbumin expressing interneurons by 8 weeks post-mitosis and act to suppress the
dentate gyrus excitability through activation of inhibitory circuits. If abGCs born in response to injury fail to
integrate into their respective inhibitory networks, then they may contribute to dysfunctional inhibition,
hyperexcitability, and altered memory processing in the dentate gyrus following TBI. Specifically, pattern
separation, a dentate-dependent memory function necessary to distinguish overlapping spatial and physical
information, relies on neurogenesis and sparse dentate activity levels. Normal pattern separation function is
largely mediated by abGC coupling to feedback inhibition in the dentate gyrus and is drastically hindered
following TBI. I hypothesize that TBI-induced abGCs are dysfunctional in their coupling to feedback inhibition
and contribute to pattern separation deficits after brain injury. The proposed study will use the Fluid Percussion
Injury (FPI) model of TBI which induces greater hippocampal neuropathology than cortical impact, and examine
morphology, migration, and electrophysiological properties of TBI-induced abGCs at the 8 week post-injury time
point. In-vivo and ex-vivo optogenetic manipulation of TBI-induced abGCs will be performed to analyze their
contribution to network excitability and functional synapses onto target neurons respectively. TBI-induced abGC
contribution to pattern separation deficit will be examined through optogenetic suppression during a hippocampal
dentate-specific spontaneous location recognition task. The results of this study will resolve controversies about
the role of injury-induced dysfunctional abGCs in dentate excitability and pattern separation deficits in response
to injury.

## Key facts

- **NIH application ID:** 9989650
- **Project number:** 5F31NS110220-02
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** Lucas Corrubia
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $39,130
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989650

## Citation

> US National Institutes of Health, RePORTER application 9989650, Role of hippocampal adult-born granule cells in TBI-induced dentate gyrus circuit pathology and pattern separation deficit (5F31NS110220-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9989650. Licensed CC0.

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