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FXR1 regulation of parvalbumin interneurons in the prefrontal cortex is critical for schizophrenia-like behaviors

Parvalbumin interneurons (PVIs) are affected in many psychiatric disorders including schizophrenia (SCZ), however the mechanism remains unclear. FXR1, a high confident risk gene for SCZ, is indispensable but its role in the brain is largely unknown. We show that deleting FXR1 from PVIs of medial pre...

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Autores principales: Shen, Minjie, Guo, Yu, Dong, Qiping, Gao, Yu, Stockton, Michael E., Li, Meng, Kannan, Sudharsan, Korabelnikov, Tomer, Schoeller, Keegan A., Sirois, Carissa L., Zhou, Chen, Le, Jonathan, Wang, Daifeng, Chang, Qiang, Sun, Qian-Quan, Zhao, Xinyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521570/
https://www.ncbi.nlm.nih.gov/pubmed/33863995
http://dx.doi.org/10.1038/s41380-021-01096-z
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author Shen, Minjie
Guo, Yu
Dong, Qiping
Gao, Yu
Stockton, Michael E.
Li, Meng
Kannan, Sudharsan
Korabelnikov, Tomer
Schoeller, Keegan A.
Sirois, Carissa L.
Zhou, Chen
Le, Jonathan
Wang, Daifeng
Chang, Qiang
Sun, Qian-Quan
Zhao, Xinyu
author_facet Shen, Minjie
Guo, Yu
Dong, Qiping
Gao, Yu
Stockton, Michael E.
Li, Meng
Kannan, Sudharsan
Korabelnikov, Tomer
Schoeller, Keegan A.
Sirois, Carissa L.
Zhou, Chen
Le, Jonathan
Wang, Daifeng
Chang, Qiang
Sun, Qian-Quan
Zhao, Xinyu
author_sort Shen, Minjie
collection PubMed
description Parvalbumin interneurons (PVIs) are affected in many psychiatric disorders including schizophrenia (SCZ), however the mechanism remains unclear. FXR1, a high confident risk gene for SCZ, is indispensable but its role in the brain is largely unknown. We show that deleting FXR1 from PVIs of medial prefrontal cortex (mPFC) leads to reduced PVI excitability, impaired mPFC gamma oscillation, and SCZ-like behaviors. PVI-specific translational profiling reveals that FXR1 regulates the expression of Cacna1h/Cav3.2 a T-type calcium channel implicated in autism and epilepsy. Inhibition of Cav3.2 in PVIs of mPFC phenocopies whereas elevation of Cav3.2 in PVIs of mPFC rescues behavioral deficits resulted from FXR1 deficiency. Stimulation of PVIs using a gamma oscillation-enhancing light flicker rescues behavioral abnormalities cause by FXR1 deficiency in PVIs. This work unveils the function of a newly identified SCZ risk gene in SCZ-relevant neurons and identifies a therapeutic target and a potential non-invasive treatment for psychiatric disorders.
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spelling pubmed-85215702022-01-16 FXR1 regulation of parvalbumin interneurons in the prefrontal cortex is critical for schizophrenia-like behaviors Shen, Minjie Guo, Yu Dong, Qiping Gao, Yu Stockton, Michael E. Li, Meng Kannan, Sudharsan Korabelnikov, Tomer Schoeller, Keegan A. Sirois, Carissa L. Zhou, Chen Le, Jonathan Wang, Daifeng Chang, Qiang Sun, Qian-Quan Zhao, Xinyu Mol Psychiatry Article Parvalbumin interneurons (PVIs) are affected in many psychiatric disorders including schizophrenia (SCZ), however the mechanism remains unclear. FXR1, a high confident risk gene for SCZ, is indispensable but its role in the brain is largely unknown. We show that deleting FXR1 from PVIs of medial prefrontal cortex (mPFC) leads to reduced PVI excitability, impaired mPFC gamma oscillation, and SCZ-like behaviors. PVI-specific translational profiling reveals that FXR1 regulates the expression of Cacna1h/Cav3.2 a T-type calcium channel implicated in autism and epilepsy. Inhibition of Cav3.2 in PVIs of mPFC phenocopies whereas elevation of Cav3.2 in PVIs of mPFC rescues behavioral deficits resulted from FXR1 deficiency. Stimulation of PVIs using a gamma oscillation-enhancing light flicker rescues behavioral abnormalities cause by FXR1 deficiency in PVIs. This work unveils the function of a newly identified SCZ risk gene in SCZ-relevant neurons and identifies a therapeutic target and a potential non-invasive treatment for psychiatric disorders. 2021-11 2021-04-16 /pmc/articles/PMC8521570/ /pubmed/33863995 http://dx.doi.org/10.1038/s41380-021-01096-z Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Shen, Minjie
Guo, Yu
Dong, Qiping
Gao, Yu
Stockton, Michael E.
Li, Meng
Kannan, Sudharsan
Korabelnikov, Tomer
Schoeller, Keegan A.
Sirois, Carissa L.
Zhou, Chen
Le, Jonathan
Wang, Daifeng
Chang, Qiang
Sun, Qian-Quan
Zhao, Xinyu
FXR1 regulation of parvalbumin interneurons in the prefrontal cortex is critical for schizophrenia-like behaviors
title FXR1 regulation of parvalbumin interneurons in the prefrontal cortex is critical for schizophrenia-like behaviors
title_full FXR1 regulation of parvalbumin interneurons in the prefrontal cortex is critical for schizophrenia-like behaviors
title_fullStr FXR1 regulation of parvalbumin interneurons in the prefrontal cortex is critical for schizophrenia-like behaviors
title_full_unstemmed FXR1 regulation of parvalbumin interneurons in the prefrontal cortex is critical for schizophrenia-like behaviors
title_short FXR1 regulation of parvalbumin interneurons in the prefrontal cortex is critical for schizophrenia-like behaviors
title_sort fxr1 regulation of parvalbumin interneurons in the prefrontal cortex is critical for schizophrenia-like behaviors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521570/
https://www.ncbi.nlm.nih.gov/pubmed/33863995
http://dx.doi.org/10.1038/s41380-021-01096-z
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