Language

English

Publication Date

5-28-2024

Journal

Cell Reports

DOI

10.1016/j.celrep.2024.114257

PMID

38761373

PMCID

PMC11234887

PubMedCentral® Posted Date

7-10-2024

PubMedCentral® Full Text Version

Author MSS

Abstract

Spiny projection neurons (SPNs) of the striatum are critical in integrating neurochemical information to coordinate motor and reward-based behavior. Mutations in the regulatory transcription factors expressed in SPNs can result in neurodevelopmental disorders (NDDs). Paralogous transcription factors Foxp1 and Foxp2, which are both expressed in the dopamine receptor 1 (D1) expressing SPNs, are known to have variants implicated in NDDs. Utilizing mice with a D1-SPN-specific loss of Foxp1, Foxp2, or both and a combination of behavior, electrophysiology, and cell-type-specific genomic analysis, loss of both genes results in impaired motor and social behavior as well as increased firing of the D1-SPNs. Differential gene expression analysis implicates genes involved in autism risk, electrophysiological properties, and neuronal development and function. Viral-mediated re-expression of Foxp1 into the double knockouts is sufficient to restore electrophysiological and behavioral deficits. These data indicate complementary roles between Foxp1 and Foxp2 in the D1-SPNs.

Keywords

Animals, Forkhead Transcription Factors, Mice, Corpus Striatum, Repressor Proteins, Mice, Knockout, Receptors, Dopamine D1, Male, Neurons, Mice, Inbred C57BL, Social Behavior

Published Open-Access

yes

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Graphical Abstract

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