# Stabilizing the tripartite synaptic complex following TBI

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2023 · $52,214

## Abstract

Summary:
Human consciousness and cognitive function are governed by a complex brain circuitry made up of neural
connections regulated by an integrated multicellular network. Glial make up 90% of all cells in the brain and play
dynamic and active roles in neuronal signaling, where astrocytes and microglia regulate synaptic transmission
and plasticity. In the past decade, increasing evidence suggests that the principal co-agonist for N-methyl-D-
Aspartate receptors (NMDARs) is the D-amino acid, D-serine, rather than glycine; however, few studies have
examined its role in CNS pathologies. To address this gap, we have recently identified a novel mechanism of
synaptic damage, where glia within the tripartite synapse uniquely synthesize and release D-serine following the
onset of pathological events. We hypothesize that microglia are a key source of pathological D-serine that
hyperactivates extrasynaptic NMDAR subunits to initiate synaptic damage as a result of microglia targeting and
pruning of dendritic spines. Our proposed experiments will examine (1) the mechanisms of D-serine release from
microglia; (2) the mechanisms of synaptic damage and microglia targeting & pruning; (3) transcriptomic analysis
of brain injury in both murine and human models. We will achieve this by employing both genetic and
pharmacological approaches to dissect the mechanism of microglial action within the complexity of brain injury
using state-of-the-art transcriptomic, imaging, and genetic techniques. Our studies will result in a better
understanding of the mechanisms that regulate synaptic damage and dysfunction, but also will start to define
novel therapeutics for patient interventions.

## Key facts

- **NIH application ID:** 10844877
- **Project number:** 3R01NS098740-06A1S1
- **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:** 2023
- **Award amount:** $52,214
- **Award type:** 3
- **Project period:** 2023-07-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10844877

## Citation

> US National Institutes of Health, RePORTER application 10844877, Stabilizing the tripartite synaptic complex following TBI (3R01NS098740-06A1S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10844877. Licensed CC0.

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