# Exploring corticostriatal dynamics associated with action control deficits in Neurexin1 alpha mutant mice

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2024 · $48,974

## Abstract

Project Summary:
 A number of neurodevelopmental disorders including autism spectrum disorder, attention-
deficit/hyperactivity disorder and Tourette syndrome exhibit characteristic motor-related symptoms such as
repetitive or impulsive action patterns. It is possible that these behaviors are a result of dysregulated action
control mechanisms mediated via cortico-basal-thalamic pathway disruption. However, it is not currently
understood how alterations in these circuits give rise to the deficits in action control commonly observed in these
disorders. Copy number variation of genes encoding for synaptic adhesion molecules, such as Neurexin1α
(Νrxn1α), have been shown to confer a significantly increased risk for these disorders, however, the underlying
neural etiopathology is currently unknown. Recent findings in acute striatal slices have revealed that loss of
Νrxn1α function results in decreased synaptic strength of medial prefrontal cortical inputs to the indirect pathway
of the dorsal striatum, providing a potential neural mechanism for irregular action control. However, it is unclear
whether these synaptic deficits confer variations to larger scale neural dynamics related to action control
dysfunction in vivo. I hypothesize that these Νrxn1α mutations drive action control deficits (Aim 1) via
mutation-associated corticostriatal circuit alterations specific to the indirect pathway (Aim 2) in Nrxn1a
KO mice. To assay multiple key aspects of action control, I will employ a novel treadmill-based operant task that
allows for the comprehensive study of action initiation, suppression, and modulation. Using dual-site in vivo
electrophysiological techniques, I plan to describe the underlying corticostriatal population recruitment related to
task performance in two fronto-striatal circuits (mPFC→DMS and M2→DLS) in both Νrxn1α WT and Νrxn1α KO
mice. These findings will provide valuable insight into the neural pathology involved in many neuropsychiatric
and neurodevelopmental disorders as well as elucidate corticostriatal neural mechanisms involved in action
control regulation.

## Key facts

- **NIH application ID:** 10874379
- **Project number:** 5F31NS130989-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Sarah Ferrigno
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 5
- **Project period:** 2023-01-04 → 2025-11-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10874379

## Citation

> US National Institutes of Health, RePORTER application 10874379, Exploring corticostriatal dynamics associated with action control deficits in Neurexin1 alpha mutant mice (5F31NS130989-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10874379. Licensed CC0.

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