# Molecular, synaptic and circuit basis for 14-3-3 dysfunction-induced behavioral deficits

> **NIH NIH R01** · FLORIDA STATE UNIVERSITY · 2021 · $378,796

## Abstract

Project Summary/Abstract:
Precise control of synaptic development and connectivity is essential for normal brain functions. Defects in
synaptic transmissions lead to the disruption of neuronal circuits, which are the underlying cause of various
neuropsychiatric diseases. To understand the in vivo functions of key synaptic regulatory proteins, we have
conducted studies on a new mouse model for 14-3-3, which is a family of brain-rich proteins implicated in
synaptic functions and genetically linked to schizophrenia. We found that inhibition of 14-3-3 functions in the
mouse brain impairs synaptic transmission, and causes a variety of behavioral deficits that correspond to the
core endophenotypes of established schizophrenia mouse models. We further identified the NMDA receptor as
one of the potential targets of 14-3-3 signaling at excitatory synapses in forebrain neurons.
These findings are exciting and suggest that mouse models of 14-3-3 dysfunction may provide unique tools to
elucidate synaptic mechanisms underlying the development of schizophrenia-associated behaviors. In this
proposal, we will 1) develop more precise animal models to define the brain regional- and developmental-
specific contributions of 14-3-3 dysfunctions to behavioral deficits; 2) determine the impact of 14-3-3
dysfunctions on neuronal excitability, synaptic physiology and synchronized network activity in the mouse
brain; and 3) delineate the cellular and molecular mechanisms underlying 14-3-3-dependent regulation of
synaptic NMDA receptors.
This research encompasses expertise, strength and existing resources in our three laboratories. Results from
this study will significantly advance our understanding on the synaptic functions of 14-3-3 proteins and their
role in mental disorders.

## Key facts

- **NIH application ID:** 10212908
- **Project number:** 5R01MH115188-05
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** YI ZHOU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $378,796
- **Award type:** 5
- **Project period:** 2017-09-18 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212908

## Citation

> US National Institutes of Health, RePORTER application 10212908, Molecular, synaptic and circuit basis for 14-3-3 dysfunction-induced behavioral deficits (5R01MH115188-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10212908. Licensed CC0.

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