# Stabilizing the Tripartite Synaptic Complex Following TBI

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2021 · $496,948

## Abstract

Summary: Traumatic brain injury (TBI) is a devastating worldwide disorder, and is believed to become the
third most prevalent health concern contributing to patient mortality by 2020. Trauma to the human brain is an
extremely difficult problem that arises from numerous factors including; brain complexity, TBI diversity,
numerous cellular targets, and the progressive nature of the injury. Our ability to model TBI in animals is critical
for developing therapeutic strategies to minimize damage and/or promote recovery. One common feature of
TBI, ranging from concussive to penetrating injuries, is diffuse and progressive synaptic damage that ultimately
leads to functional losses. Our studies will model synaptic damage in the absence of neuron losses in the
hippocampus to examine mechanisms of action that underlie progressive synaptic damage. We hypothesize
that the phasic release of the co-transmitter D-serine from hippocampal glutaminergic neurons plays an
important role in regulating synaptic function; however, following injury D-serine is suppressed in neurons but
up regulated in astrocytes. Increased tonic release of astrocytic D-serine leads to sub-lethal excititoxic synaptic
damage over the first week post-injury. We have also found that enhanced astrocytic D-serine levels are
regulated by neuronal-astrocyte communication in the tripartite synapse. Specifically, we hypothesize that
neuronal ephrinB3 communicates with astrocytic EphB3 and EphA4 to regulate D-serine production and
release. Following TBI, increased levels of Eph signaling in reactive astrocytes results in excessive release of
D-serine. Our studies take a comprehensive approach to address our hypotheses using cutting edge
techniques and cell specific knockout and knockin mice to investigate the mechanisms that regulate D-serine
mediated synaptic function and dysfunction.

## Key facts

- **NIH application ID:** 10074600
- **Project number:** 5R01NS098740-05
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Daniel Jon Liebl
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $496,948
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074600

## Citation

> US National Institutes of Health, RePORTER application 10074600, Stabilizing the Tripartite Synaptic Complex Following TBI (5R01NS098740-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10074600. Licensed CC0.

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