# Functions of ERK/MAPK Signaling in GABAergic Circuit Development

> **NIH NIH R01** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2020 · $340,689

## Abstract

Project Summary/Abstract
 The ERK/MAPK intracellular signal transduction cascade is activated by extracellular stimuli that play
important roles in nervous system development and plasticity. Genetic disruption of ERK/MAPK signaling has
been implicated in neurodevelopmental syndromes that involve intellectual disability, learning abnormalities,
neurodevelopmental delay, and seizures. Perturbations in ERK/MAPK activity have also been observed in
genetic models of autism spectrum disorders, pediatric traumatic brain injury, neonatal hypoxia-ischemia, and
childhood epilepsy. GABAergic circuit dysfunction is thought to contribute to the pathogenesis of many of these
conditions. However, our understanding of the functions of ERK/MAPK in the initial development of the
GABAergic system is poorly understood. This proposal brings together an interdisciplinary team to define the
precise role of ERK/MAPK in GABAergic circuit formation and function using a combination of unique genetically
modified rodent models, high-resolution confocal microscopy, patch-clamp electrophysiology, high-throughput
sequencing, chemogenetic tools, and behavioral analyses. We will delineate changes in cellular development,
synaptic strength, activity dependent gene expression, and behavior in ERK/MAPK mutant mouse models that
exhibits specific deficits in GABAergic circuits. Finally, we will begin to explore pharmacological and activity-
modulating approaches to reverse GABAergic defects in ERK/MAPK mutant mice. These data will provide
unique insight into the pathophysiology of conditions resulting from perturbation of ERK/MAPK in the brain and
help guide the development of new therapeutic strategies.

## Key facts

- **NIH application ID:** 9923769
- **Project number:** 5R01NS097537-05
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** Jason Marshall Newbern
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $340,689
- **Award type:** 5
- **Project period:** 2016-07-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9923769

## Citation

> US National Institutes of Health, RePORTER application 9923769, Functions of ERK/MAPK Signaling in GABAergic Circuit Development (5R01NS097537-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9923769. Licensed CC0.

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