# GluN2B Associated Neurodevelopmental Disorders

> **NIH NIH R03** · STATE UNIVERSITY NEW YORK STONY BROOK · 2020 · $76,451

## Abstract

PROJECT SUMMARY/ABSTRACT
NMDA receptors (NMDARs) are glutamate-gated ion channels that mediate excitatory
neurotransmission in the brain. Many higher order neural processes including synaptogenesis
and the synaptic plasticity underlining learning and memory depend on NMDAR-mediated
transmission. The NMDAR GluN2B subunit is critically involved in early brain development.
Accordingly, missense and nonsense mutations in GRIN2B, the gene encoding GluN2B, are
associated with autism spectrum disorder, intellectual disability, and schizophrenia among other
neurodevelopmental disorders. The specific role of GluN2B in brain development and the causal
link between GluN2B dysfunction and these diverse disorders is unknown. Our goal, taking
advantage of the power of zebrafish, is to identify the role of GluN2B in brain development and
neurodevelopmental disorders and to pioneer new therapies to treat such disorders. We must
first establish the use of zebrafish as a model system to study GluN2B in neurodevelopmental
disorders. To do so, we will test whether zebrafish GluN2B (zGluN2B) functions similarly to
human GluN2B and if it displays a comparable pharmacology (Aim#1). In addition, we need to
identify GluN2B-dependent zebrafish behaviors (Aim#2), which provide a pathway to study
circuit development and a substrate for behaviorally-based drug screens. In Aim 1, we will use
heterologous expression zebrafish and human NMDAR subunits in HEK293 cells and patch
clamp electrophysiology to characterize functional and pharmacological properties. In Aim 2, we
will examine how knockout of zebrafish GluN2B affects behaviors associated with human
neurodevelopmental disorders. In the long-term, zebrafish have the potential to provide a
platform to study the role of GluN2B in brain development and the effects of human GRIN2B
missense mutations on neural circuit development and carry out behaviorally based high
throughput small molecule drug screens to counter the effects of GluN2B dysfunction.

## Key facts

- **NIH application ID:** 9954586
- **Project number:** 1R03HD101767-01
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** HOWARD I SIROTKIN
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $76,451
- **Award type:** 1
- **Project period:** 2020-05-19 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9954586

## Citation

> US National Institutes of Health, RePORTER application 9954586, GluN2B Associated Neurodevelopmental Disorders (1R03HD101767-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9954586. Licensed CC0.

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