{"doi":"10.1101/2023.06.24.546368","title":"Repeat investigation during social preference behavior is suppressed in male mice with prefrontal cortex <i>cacna1c</i> (Ca <sub>v</sub> 1.2)-deficiency through the dysregulation of neural dynamics","abstract":"Abstract Impairments in social behavior are observed in a range of neuropsychiatric disorders and several lines of evidence have demonstrated that dysfunction of the prefrontal cortex (PFC) plays a central role in social deficits. We have previously shown that loss of neuropsychiatric risk gene Cacna1c that codes for the Ca v 1.2 isoform of L-type calcium channels (LTCCs) in the PFC result in impaired sociability as tested using the three-chamber social approach test. In this study we aimed to further characterize the nature of the social deficit associated with a reduction in PFC Ca v 1.2 channels (Cav1.2 PFCKO mice) by testing male mice in a range of social and non-social tests while examining PFC neural activity using in vivo GCaMP6s fiber photometry. We found that during the first investigation of the social and non-social stimulus in the three-chamber test, both Ca v 1.2 PFCKO male mice and Ca v 1.2 PFCGFP controls spent significantly more time with the social stimulus compared to a non-social object. In contrast, during repeat investigations while Ca v 1.2 PFCWT mice continued to spend more time with the social stimulus, Ca v 1.2 PFCKO mice spent equal amount of time with both social and non-social stimuli. Neural activity recordings paralleled social behavior with increase in PFC population activity in Ca v 1.2 PFCWT mice during first and repeat investigations, which was predictive of social preference behavior. In Ca v 1.2 PFCKO mice, there was an increase in PFC activity during first social investigation but not during repeat investigations. These behavioral and neural differences were not observed during a reciprocal social interaction test nor during a forced alternation novelty test. To evaluate a potential deficit in reward-related processes, we tested mice in a three-chamber test wherein the social stimulus was replaced by food. Behavioral testing revealed that both Ca v 1.2 PFCWT and Ca v 1.2 PFCKO mice showed a preference for food over object with significantly greater preference during repeat investigation. Interestingly, there was no increase in PFC activity when Ca v 1.2 PFCWT or Ca v 1.2 PFCKO first investigated the food however activity significantly increased in Ca v 1.2 PFCWT mice during repeat investigations of the food. This was not observed in Ca v 1.2 PFCKO mice. In summary, a reduction in Ca v 1.2 channels in the PFC suppresses the development of a sustained social preference in mice that is associated with lack of PFC neuronal population activity that may be related to deficits in social reward.","journal":"Publicaciones de la Facultad de Educación y Humanidades del Campus de Melilla","year":2023,"id":399933,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1042997,"name":"Viraj Nadkarni","orcid":"0000-0002-2319-4931","position":1,"is_corresponding":false},{"id":1176266,"name":"R. Singh","orcid":"0009-0004-5016-9610","position":2,"is_corresponding":false},{"id":1176611,"name":"Camille L. Carthy","orcid":null,"position":3,"is_corresponding":false},{"id":1042998,"name":"Susan A. Antigua","orcid":"0000-0001-5954-5716","position":4,"is_corresponding":false},{"id":1042995,"name":"Baila S. Hall","orcid":"0000-0002-1171-2295","position":5,"is_corresponding":false},{"id":344892,"name":"Anjali M. Rajadhyaksha","orcid":"0000-0002-8399-5466","position":6,"is_corresponding":false},{"id":440211,"name":"Jonathan Hackett","orcid":"0000-0003-4965-2045","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T01:20:00.023537Z","pmid":"37425963","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":[]}