{"doi":"10.1016/j.bpsgos.2025.100537","title":"The Impact of Overexpression of the Mouse Ortholog of CACNA1C on Behavior and Cortical Dynamics","abstract":"Background Mental disorders are common in the United States (US). According to the National Institute of Mental Health more than 23% of the adult population in the US live with some form of mental illness. Genome-wide association studies have implicated CACNA1C which encodes the L-type voltage gated calcium channel Ca V 1.2 and it has been suggested that the expression levels of CACNA1C may be associated with mental illness. To this end, we have generated a novel mouse line that conditionally overexpresses the mouse ortholog Cacna1c . Methods Transgenic mice (Ca V 1.2 Tg+ mice) were characterized for expression and distribution of Ca V 1.2. The Ca V 1.2 Tg+ mice were compared to control littermates using assays which examined cognitive and affective behaviors. Cortical network dynamics were assessed using in vivo multi-photon calcium imaging. Results Compared to their control littermates, Ca V 1.2 Tg+ mice exhibited a ∼ 1-fold increase in Ca V 1.2 expression. Behavioral characterization of the Ca V 1.2 Tg+ mice revealed a complex phenotype in which they exhibited deficits in the consolidation of fearful memories and an increase in anxiolytic-like behavior. The Ca V 1.2 Tg+ mice also appear to have altered cortical dynamics in which the network is more dense but less synchronized. Conclusions We have successfully generated mice that over express the mouse ortholog of a gene which has been implicated in several psychiatric diseases. Our initial characterization suggests that these mice have alterations in behavior and neural function that have been linked to mental illness. It is anticipated that additional studies will reveal additional neurobehavioral alterations whose mechanisms will be studied.","journal":"Biological Psychiatry Global Open Science","year":2025,"id":566533,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":380542,"name":"Ruei‐Lung Lin","orcid":"0000-0001-9041-284X","position":1,"is_corresponding":false},{"id":456024,"name":"Lara Ouillette","orcid":null,"position":2,"is_corresponding":false},{"id":865455,"name":"Emily Glass","orcid":null,"position":3,"is_corresponding":false},{"id":1470591,"name":"Hannah Burns","orcid":null,"position":4,"is_corresponding":false},{"id":916297,"name":"Michael D. Uhler","orcid":"0000-0002-2518-8308","position":5,"is_corresponding":false},{"id":940064,"name":"Sami L. Case","orcid":"0000-0002-1004-7246","position":6,"is_corresponding":false},{"id":380544,"name":"Olivier Thibault","orcid":"0000-0002-3548-3466","position":7,"is_corresponding":false},{"id":455504,"name":"Geoffrey G. Murphy","orcid":"0000-0003-3691-1722","position":8,"is_corresponding":false},{"id":456026,"name":"Rachel Parent","orcid":null,"position":0,"is_corresponding":true}],"reference_count":86,"raw_metadata":null,"created_at":"2026-07-19T02:56:36.440192Z","pmid":"40678692","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}