# Molecular Analysis of Developmental Brain Disorders Associated with Synaptic Pathology

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $575,925

## Abstract

ABSTRACT
Synapses are the most abundant and distinguishing feature of the brain, providing enormous functional
diversity and plasticity to neural circuits. These structures are incredibly small, less than 1 femtoliter in
volume, and remarkably plastic in their functional properties. Unique ensembles of protein networks that are
enriched within postsynaptic structures orchestrate the development, maintenance, and plasticity of
synapses. Genetic mutations associated with risk for intellectual disability, schizophrenia, autism, and other
developmental brain disorders (DBDs) are predominated by genes encoding synaptic proteins. These
observations have led to the hypothesis that many DBDs are synaptopathologies that alter synaptic
development and function. However, while histological evidence in human postmortem samples and mouse
models supports this theory, the molecular mechanisms of synaptic pathology remain poorly understood.
This proposal will address this gap in knowledge by combining recent advances in CRISPR-genome editing
paired with two highly innovative proteomics approaches we have developed to enable: 1) the discovery of
synaptic protein complexes in vivo that are associated with DBDs and 2) how these complexes are disrupted
in diverse models of DBD. This will significantly advance our understanding of potential synaptopathic
mechanisms that may be comorbid across DBD mutations. Uncovering these molecular mechanisms of
synaptopathology can be expected to lead to better insights of disorder etiology and potential therapeutic
approaches.

## Key facts

- **NIH application ID:** 9891097
- **Project number:** 5R01MH111684-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** SCOTT H SODERLING
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $575,925
- **Award type:** 5
- **Project period:** 2017-06-16 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891097

## Citation

> US National Institutes of Health, RePORTER application 9891097, Molecular Analysis of Developmental Brain Disorders Associated with Synaptic Pathology (5R01MH111684-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9891097. Licensed CC0.

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