biostudies-literatureSmedler EHj&amp;#x00E4;rnfondenEuropean Molecular Biology OrganizationVetenskapsr&amp;#x00E5;detBarncancerfondenCancerfondene2108768119https://www.ebi.ac.uk/biostudies/studies/S-EPMC8851547biostudies-literatureUnknown119(7)The L-type voltage-gated Ca²⁺ channel gene <i>CACNA1C</i> is a risk gene for various psychiatric conditions, including schizophrenia and bipolar disorder. However, the cellular mechanism by which <i>CACNA1C</i> contributes to psychiatric disorders has not been elucidated. Here, we report that the embryonic deletion of <i>Cacna1c</i> in neurons destined for the cerebral cortex using an <i>Emx1-Cre</i> strategy disturbs spontaneous Ca²⁺ activity and causes abnormal brain development and anxiety. By combining computational modeling with electrophysiological membrane potential manipulation, we found that neural network activity was driven by intrinsic spontaneous Ca²⁺ activity in distinct progenitor cells expressing marginally increased levels of voltage-gated Proceedings of the National Academy of Sciences of the United States of AmericaDisrupted <i>Cacna1c</i> gene expression perturbs spontaneous Ca²⁺ activity causing abnormal brain development and increased anxiety.PMC8851547FO2020-0199FO2018-0209CAN 2016-8012017-0081519 0545 UsPR2020-0124ALTF 596-20142021-031082013-318919 0544 PjFO2017-0107PR2018-0123Brusini IMasini DWang CKanatani SMalmersjo SRebellato PZhang SSmedler EFisone GDehnisch Ellstrom IWest ZHarkany TLouhivuori LUhlen PRomanov RACaramia MfalseDisrupted <i>Cacna1c</i> gene expression perturbs spontaneous Ca²⁺ activity causing abnormal brain development and increased anxiety.The L-type voltage-gated Ca²⁺ channel gene <i>CACNA1C</i> is a risk gene for various psychiatric conditions, including schizophrenia and bipolar disorder. However, the cellular mechanism by which <i>CACNA1C</i> contributes to psychiatric disorders has not been elucidated. Here, we report that the embryonic deletion of <i>Cacna1c</i> in neurons destined for the cerebral cortex using an <i>Emx1-Cre</i> strategy disturbs spontaneous Ca²⁺ activity and causes abnormal brain development and anxiety. By combining computational modeling with electrophysiological membrane potential manipulation, we found that neural network activity was driven by intrinsic spontaneous Ca²⁺ activity in distinct progenitor cells expressing marginally increased levels of voltage-gated 2022-01-01T00:00:00Z2022 Feb2025-06-01T04:20:18.592Z2025-06-01T04:20:18.592ZS-EPMC88515473513587510.1073/pnas.2108768119