# Evaluating a cell type-specific mechanism of glutamatergic synapse function and organization

> **NIH MH F31** · TUFTS UNIVERSITY BOSTON · 2026 · $46,302

## Abstract

Project Summary/Abstract
 Impaired inhibitory signaling underlies the development of various neuropsychiatric disorders including
anxiety, epilepsy, autism, and schizophrenia. Inhibition is mediated by interneurons (INs), a small but diverse
population of cells that coordinates network activity of principal neuron underlying cognition. Glutamatergic
excitation of INs determines subsequent firing and control of downstream circuits, and glutamatergic synapses
received by INs have unique basal transmission properties and exhibit distinct synaptic plasticity compared to
excitatory neurons. These differences in functionality are likely due to cell-type specific differences in
postsynaptic density (PSD) composition and maintenance mechanisms. For example, recently identified
postsynaptic proteins such as Btbd11 which are expressed exclusively in glutamatergic IN-PSD could underly
the unique synaptic properties seen in INs. Growing evidence supports the idea that the PSD is organized
through liquid-liquid phase separation (LLPS), the process of maintaining protein-dense, membrane-less
organelles. Btbd11 has been shown to i) regulate synaptic function in INs and ii) undergo LLPS with key
glutamatergic scaffolding proteins. However, whether Btbd11’s regulation of glutamatergic synapses requires
LLPS is not yet known, and the extent to which Btbd11 mediates synaptic composition has not been explored.
 To investigate how the protein composition of glutamatergic IN-PSD contributes to the unique function of
INs and subsequent role in pathophysiology, this application will utilize molecular biology, proteomic
analysis, live cellular imaging and electrophysiology to address the novel hypothesis that Btbd11
promotes glutamatergic IN-PSD function through stabilizing interactions with Psd-95 and associated
protein complexes via LLPS. In Aim 1, we will examine how Btbd11 ablation alters the IN-PSD proteome and
levels of glutamatergic signaling molecules to determine a role in synaptic

## Key facts

- **NIH application ID:** 11324914
- **Project number:** 5F31MH140553-02
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Molly Brady Boyer
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** MH
- **Fiscal year:** 2026
- **Award amount:** $46,302
- **Award type:** 5
- **Project period:** 2025-05-01T00:00:00 → 2027-10-23T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11324914

## Citation

> US National Institutes of Health, RePORTER application 11324914, Evaluating a cell type-specific mechanism of glutamatergic synapse function and organization (5F31MH140553-02). Retrieved via AI Analytics 2026-07-02 from https://api.ai-analytics.org/grant/nih/11324914. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*