Open AccessDisrupted Cacna1c gene expression perturbs spontaneous Ca 2+ activity causing abnormal brain development and increased anxiety
Author(s) -
Erik Smedler,
Lauri Louhivuori,
Roman A. Romanov,
Débora Masini,
Ivar Dehnisch Ellström,
Chungliang Wang,
Martino Caramia,
Zoe Elizabeth West,
Songbai Zhang,
Paola Rebellato,
Seth Malmersjö,
Irene Brusini,
Shigeaki Kanatani,
Gilberto Fisone,
Tibor Harkany,
Per Uhlén
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2108768119
Subject(s) - gene expression , anxiety , gene , microbiology and biotechnology , biology , chemistry , psychology , genetics , psychiatry
Significance The geneCACNA1C encodes for a calcium channel that has been linked to various psychiatric conditions, including schizophrenia and bipolar disorder, through hitherto unknown cellular mechanisms. Here, we report that deletion ofCacna1c in neurons of the developing brain disrupts spontaneous calcium activity and causes abnormal brain development and anxiety. Our results indicate that marginally alterations in the expression level ofCacna1c have major effects on the intrinsic spontaneous calcium activity of neural progenitors that play a crucial role in brain development. Thus,Cacna1c acts as a molecular switch that can increase susceptibility to psychiatric disease.