The Impact of Overexpression of the Mouse Ortholog of CACNA1C on Behavior and Cortical Dynamics
Background: Mental disorders are common in the United States. According to the National Institute of Mental Health more than 23% of the adult population in the United States live with some form of mental illness. Genome-wide association studies have implicated CACNA1C, which encodes the L-type volta...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-09-01
|
| Series: | Biological Psychiatry Global Open Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667174325000916 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1839643117516488704 |
|---|---|
| author | Rachel Parent Ruei-Lung Lin Lara Ouillette Emily Glass Hannah Burns Michael D. Uhler Sami L. Case Olivier Thibault Geoffrey G. Murphy |
| author_facet | Rachel Parent Ruei-Lung Lin Lara Ouillette Emily Glass Hannah Burns Michael D. Uhler Sami L. Case Olivier Thibault Geoffrey G. Murphy |
| author_sort | Rachel Parent |
| collection | DOAJ |
| description | Background: Mental disorders are common in the United States. According to the National Institute of Mental Health more than 23% of the adult population in the United States live with some form of mental illness. Genome-wide association studies have implicated CACNA1C, which encodes the L-type voltage-gated calcium channel CaV1.2, 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 (CaV1.2Tg+ mice) were characterized for expression and distribution of CaV1.2. The CaV1.2Tg+ mice were compared with control littermates using assays that examined cognitive and affective behaviors. Cortical network dynamics were assessed using in vivo multiphoton calcium imaging. Results: Compared with their control littermates, CaV1.2Tg+ mice exhibited a ∼1-fold increase in CaV1.2 expression. Behavioral characterization of the CaV1.2Tg+ mice revealed a complex phenotype in which they exhibited deficits in the consolidation of fearful memories and an increase in anxiolytic-like behavior. The CaV1.2Tg+ mice also appeared to have altered cortical dynamics in which the network was more dense but less synchronized. Conclusions: We have successfully generated mice that overexpress the mouse ortholog of a gene that 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 future studies will reveal additional neurobehavioral alterations whose mechanisms will be studied. |
| format | Article |
| id | doaj-art-f1654a43e32b4c2887bc3f39d0b4042f |
| institution | Matheson Library |
| issn | 2667-1743 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biological Psychiatry Global Open Science |
| spelling | doaj-art-f1654a43e32b4c2887bc3f39d0b4042f2025-07-02T04:50:55ZengElsevierBiological Psychiatry Global Open Science2667-17432025-09-0155100537The Impact of Overexpression of the Mouse Ortholog of CACNA1C on Behavior and Cortical DynamicsRachel Parent0Ruei-Lung Lin1Lara Ouillette2Emily Glass3Hannah Burns4Michael D. Uhler5Sami L. Case6Olivier Thibault7Geoffrey G. Murphy8Michigan Neuroscience Institute, Michigan Medicine University of Michigan, Ann Arbor, MichiganPharmacology and Nutritional Sciences, University of Kentucky, Lexington, KentuckyMichigan Neuroscience Institute, Michigan Medicine University of Michigan, Ann Arbor, MichiganMichigan Neuroscience Institute, Michigan Medicine University of Michigan, Ann Arbor, MichiganMichigan Neuroscience Institute, Michigan Medicine University of Michigan, Ann Arbor, MichiganMichigan Neuroscience Institute, Michigan Medicine University of Michigan, Ann Arbor, Michigan; Department of Biological Chemistry, Michigan Medicine University of Michigan, Ann Arbor, MichiganPharmacology and Nutritional Sciences, University of Kentucky, Lexington, KentuckyPharmacology and Nutritional Sciences, University of Kentucky, Lexington, KentuckyMichigan Neuroscience Institute, Michigan Medicine University of Michigan, Ann Arbor, Michigan; Department of Molecular & Integrative Physiology, Michigan Medicine University of Michigan, Ann Arbor, Michigan; Address correspondence to Geoffrey G. Murphy, Ph.D.Background: Mental disorders are common in the United States. According to the National Institute of Mental Health more than 23% of the adult population in the United States live with some form of mental illness. Genome-wide association studies have implicated CACNA1C, which encodes the L-type voltage-gated calcium channel CaV1.2, 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 (CaV1.2Tg+ mice) were characterized for expression and distribution of CaV1.2. The CaV1.2Tg+ mice were compared with control littermates using assays that examined cognitive and affective behaviors. Cortical network dynamics were assessed using in vivo multiphoton calcium imaging. Results: Compared with their control littermates, CaV1.2Tg+ mice exhibited a ∼1-fold increase in CaV1.2 expression. Behavioral characterization of the CaV1.2Tg+ mice revealed a complex phenotype in which they exhibited deficits in the consolidation of fearful memories and an increase in anxiolytic-like behavior. The CaV1.2Tg+ mice also appeared to have altered cortical dynamics in which the network was more dense but less synchronized. Conclusions: We have successfully generated mice that overexpress the mouse ortholog of a gene that 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 future studies will reveal additional neurobehavioral alterations whose mechanisms will be studied.http://www.sciencedirect.com/science/article/pii/S2667174325000916Bipolar disorderCortical subnetworksL-type calcium channel CaV1.2Psychiatric risk variantSchizophrenia |
| spellingShingle | Rachel Parent Ruei-Lung Lin Lara Ouillette Emily Glass Hannah Burns Michael D. Uhler Sami L. Case Olivier Thibault Geoffrey G. Murphy The Impact of Overexpression of the Mouse Ortholog of CACNA1C on Behavior and Cortical Dynamics Biological Psychiatry Global Open Science Bipolar disorder Cortical subnetworks L-type calcium channel CaV1.2 Psychiatric risk variant Schizophrenia |
| title | The Impact of Overexpression of the Mouse Ortholog of CACNA1C on Behavior and Cortical Dynamics |
| title_full | The Impact of Overexpression of the Mouse Ortholog of CACNA1C on Behavior and Cortical Dynamics |
| title_fullStr | The Impact of Overexpression of the Mouse Ortholog of CACNA1C on Behavior and Cortical Dynamics |
| title_full_unstemmed | The Impact of Overexpression of the Mouse Ortholog of CACNA1C on Behavior and Cortical Dynamics |
| title_short | The Impact of Overexpression of the Mouse Ortholog of CACNA1C on Behavior and Cortical Dynamics |
| title_sort | impact of overexpression of the mouse ortholog of cacna1c on behavior and cortical dynamics |
| topic | Bipolar disorder Cortical subnetworks L-type calcium channel CaV1.2 Psychiatric risk variant Schizophrenia |
| url | http://www.sciencedirect.com/science/article/pii/S2667174325000916 |
| work_keys_str_mv | AT rachelparent theimpactofoverexpressionofthemouseorthologofcacna1conbehaviorandcorticaldynamics AT rueilunglin theimpactofoverexpressionofthemouseorthologofcacna1conbehaviorandcorticaldynamics AT laraouillette theimpactofoverexpressionofthemouseorthologofcacna1conbehaviorandcorticaldynamics AT emilyglass theimpactofoverexpressionofthemouseorthologofcacna1conbehaviorandcorticaldynamics AT hannahburns theimpactofoverexpressionofthemouseorthologofcacna1conbehaviorandcorticaldynamics AT michaelduhler theimpactofoverexpressionofthemouseorthologofcacna1conbehaviorandcorticaldynamics AT samilcase theimpactofoverexpressionofthemouseorthologofcacna1conbehaviorandcorticaldynamics AT olivierthibault theimpactofoverexpressionofthemouseorthologofcacna1conbehaviorandcorticaldynamics AT geoffreygmurphy theimpactofoverexpressionofthemouseorthologofcacna1conbehaviorandcorticaldynamics AT rachelparent impactofoverexpressionofthemouseorthologofcacna1conbehaviorandcorticaldynamics AT rueilunglin impactofoverexpressionofthemouseorthologofcacna1conbehaviorandcorticaldynamics AT laraouillette impactofoverexpressionofthemouseorthologofcacna1conbehaviorandcorticaldynamics AT emilyglass impactofoverexpressionofthemouseorthologofcacna1conbehaviorandcorticaldynamics AT hannahburns impactofoverexpressionofthemouseorthologofcacna1conbehaviorandcorticaldynamics AT michaelduhler impactofoverexpressionofthemouseorthologofcacna1conbehaviorandcorticaldynamics AT samilcase impactofoverexpressionofthemouseorthologofcacna1conbehaviorandcorticaldynamics AT olivierthibault impactofoverexpressionofthemouseorthologofcacna1conbehaviorandcorticaldynamics AT geoffreygmurphy impactofoverexpressionofthemouseorthologofcacna1conbehaviorandcorticaldynamics |