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

URL: https://www.ncbi.nlm.nih.gov/pubmed/33831348
DOI: 10.1016/j.neuron.2021.03.016

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 > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
organs, tissues, organelles, cell types and functions > tissues types and functions > prefrontal cortex
organism description > animal behavior > stress
CSHL Authors:
Communities: CSHL labs > Van Aelst lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 1 April 2021
Date Deposited: 28 Apr 2021 17:27
Last Modified: 28 Apr 2021 17:28
URI: https://repository.cshl.edu/id/eprint/39942

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