# Functional, structural, and computational consequences of NMDA receptor ablation at medial prefrontal cortex synapses

> **NIH NIH F31** · UNIVERSITY OF MINNESOTA · 2024 · $36,594

## Abstract

Project Summary
Schizophrenia is a psychiatric disorder that affects approximately 24 million people worldwide and can lead to
emotional distress, disability, and reduced lifespan. Cognitive dysfunction is the best predictor of patient outcome
in schizophrenia, yet current pharmacological treatments often fail to treat cognitive symptoms such as working
memory deficits. In addition, it is not yet understood how certain biological abnormalities associated with
schizophrenia – for example, decreased cortical expression of N-methyl-D-aspartate (NMDA) receptors – lead
to changes in brain circuit function, especially when these abnormalities progress over the course of the lifespan
and may be affected by in vivo compensatory mechanisms in the brain. My proposed research seeks to
investigate the effects of chronic NMDA receptor loss upon synaptic function and architecture in the prefrontal
cortex, and its potential implications for neural network activity and working memory deficits. Specifically, this
computational psychiatry project will focus on examining functional and structural abnormalities at excitatory-to-
excitatory synapses, which produce the reverberant neural activity that allows information to be retained in
working memory and are particularly vulnerable to disconnection in schizophrenia. I will measure functional
changes in excitatory-to-excitatory synaptic strength using ex vivo slice electrophysiology in prefrontal cortex
pyramidal neurons, and I will examine structural changes in dendritic spine morphology and density in the same
neurons using confocal imaging. I will then leverage insights gained from these electrophysiology and imaging
experiments to build and test predictions regarding stability and synchrony of brain activity in a spiking network
model.

## Key facts

- **NIH application ID:** 10909011
- **Project number:** 5F31MH133285-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Rachel Dick
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $36,594
- **Award type:** 5
- **Project period:** 2023-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909011

## Citation

> US National Institutes of Health, RePORTER application 10909011, Functional, structural, and computational consequences of NMDA receptor ablation at medial prefrontal cortex synapses (5F31MH133285-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10909011. Licensed CC0.

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