Oligophrenin-1 moderates behavioral responses to stress by regulating parvalbumin interneuron activity in the medial prefrontal cortex

Wang, Minghui, Gallo, Nicholas B, Tai, Yilin, Li, Bo, Van Aelst, Linda (April 2021) Oligophrenin-1 moderates behavioral responses to stress by regulating parvalbumin interneuron activity in the medial prefrontal cortex. Neuron. ISSN 0896-6273

Abstract

Ample evidence indicates that individuals with intellectual disability (ID) are at increased risk of developing stress-related behavioral problems and mood disorders, yet a mechanistic explanation for such a link remains largely elusive. Here, we focused on characterizing the syndromic ID gene oligophrenin-1 (OPHN1). We find that Ophn1 deficiency in mice markedly enhances helpless/depressive-like behavior in the face of repeated/uncontrollable stress. Strikingly, Ophn1 deletion exclusively in parvalbumin (PV) interneurons in the prelimbic medial prefrontal cortex (PL-mPFC) is sufficient to induce helplessness. This behavioral phenotype is mediated by a diminished excitatory drive onto Ophn1-deficient PL-mPFC PV interneurons, leading to hyperactivity in this region. Importantly, suppressing neuronal activity or RhoA/Rho-kinase signaling in the PL-mPFC reverses helpless behavior. Our results identify OPHN1 as a critical regulator of adaptive behavioral responses to stress and shed light onto the mechanistic links among OPHN1 genetic deficits, mPFC circuit dysfunction, and abnormalities in stress-related behaviors.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification organism description > animal organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > cytoskeletal proteins organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase organism description > animal > mammal organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions organs, tissues, organelles, cell types and functions > tissues types and functions > prefrontal cortex bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types organism description > animal > mammal > rodent organism description > animal behavior > stress
CSHL Authors:	Van Aelst, Linda Gallo, Nicholas Tai, Yilin Li, Bo
Communities:	CSHL labs > Van Aelst lab CSHL Cancer Center Program CSHL Cancer Center Program > Cellular Communication in Cancer Program
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	1 April 2021
Date Deposited:	28 Apr 2021 17:27
Last Modified:	13 Feb 2024 19:30
PMCID:	PMC8141044
URI:	https://repository.cshl.edu/id/eprint/39942

Actions (login required)

Administrator's edit/view item