# Interneuron Synapses: In Vivo Chemicogenetic Proteomics to Discover Developmental Brain Disorder Etiologies

> **NIH NIH F30** · DUKE UNIVERSITY · 2020 · $37,643

## Abstract

ABSTRACT:
Developmental brain disorders (DBDs), such as autism, epilepsy, and schizophrenia, are neurological disorders
associated with complex genetic etiologies. Emerging evidence strongly suggests that DBDs arise from
disturbances between neural circuit excitation and inhibition (E/I imbalance), driven by neuronal synapse
abnormalities, as well as inhibitory interneuron dysfunction. Interestingly, analyses of atypical synapse structure
and aberrant interneuron function have largely been pursued independently, primarily because the tools to
isolate and analyze interneuron synapses were non-existent. The unknown molecular composition and
modulation of interneuron synapses is a fundamental gap in neuroscience knowledge, which limits the ability to
analyze their functional contribution to DBDs. To address this critical barrier, I propose to utilize in vivo
chemicogenetic proteomics (iBioID) approach to chart, for the first time, the synaptic proteomes of the two most
prevalent genetically-defined interneuron subtypes, parvalbumin (PV) and somatostatin (SST) neurons. My
central hypothesis is that the molecular composition of synapses in these cells is unique, reflecting their
morphological and physiological differences from other synapses, such as the glutamatergic dendritic spine. I
predict that interneuron synapses serve as important nodes of DBD genetic burden, which will be revealed by
the discovery of their protein composition and molecular functions.
The long-term goal of this project is to elucidate the mechanisms of interneuron synaptic signaling in order to
identify potential novel neuropsychiatric treatment mechanisms. The primary objective of this project is to dissect
the functional role of disease-relevant synaptic molecules in PV and SST neural populations. Evaluating how
these candidate proteins interact in each synaptic environment will help determine how various DBDs converge
on similar phenotypic outputs and improve the efficacy of clinical therapies.
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## Key facts

- **NIH application ID:** 9893718
- **Project number:** 5F30MH117851-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Jamie Lynn Courtland
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,643
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893718

## Citation

> US National Institutes of Health, RePORTER application 9893718, Interneuron Synapses: In Vivo Chemicogenetic Proteomics to Discover Developmental Brain Disorder Etiologies (5F30MH117851-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9893718. Licensed CC0.

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