| First Author | Yabuki Y | Year | 2025 |
| Journal | Acta Physiol (Oxf) | Volume | 241 |
| Issue | 5 | Pages | e70043 |
| PubMed ID | 40197682 | Mgi Jnum | J:365791 |
| Mgi Id | MGI:8188266 | Doi | 10.1111/apha.70043 |
| Citation | Yabuki Y, et al. (2025) Cav3.1 T-Type Calcium Channel Acts as a Gateway for GABAergic Excitation in the Medial Prefrontal Cortex That Leads to Chronic Psychological Stress Responses in Mice. Acta Physiol (Oxf) 241(5):e70043 |
| abstractText | AIM: The molecular mechanisms of chronic stress-induced psychiatric disorders, including depression, remain unknown. The current study aimed to assess the role of Cav3.1 T-type calcium channels as a gateway for the chronic stress-induced activation of parvalbumin (PV)-positive gamma-aminobutyric acidergic (GABAergic) neurons in the medial prefrontal cortex (mPFC) of mice. METHODS: The function of the Cav3.1 T-type calcium channel in the mouse mPFC following chronic stress was investigated using behavioral tests, electrophysiological analyses, transcriptome analyses, and optogenetic approaches. RESULTS: Cav3.1-knockout (Cav3.1(-/-)) mice were resistant to chronic stress-induced depressive-like behaviors induced by repeated forced-swimming test or tail-suspension test. Immunohistochemical analysis revealed that Cav3.1 was predominantly localized in PV-positive GABAergic neurons in the mPFC. Based on transcriptomic and electrophysiological analyses, the excitatory-inhibitory (E-I) balance was disrupted by the chronic stress-induced activation of PV-positive GABAergic neurons in the mPFC of wild-type (WT) mice, but not in that of Cav3.1(-/-) mice. Optogenetic control of PV-positive GABAergic neurons in the mPFC revealed that they played a pivotal role in depressive-like behaviors. The administration of TTA-A2, a selective T-type calcium channel antagonist, reduced chronic stress-induced depressive-like behaviors. CONCLUSION: The Cav3.1 T-type calcium channel acts as a gateway for the activation of GABAergic neurons in the mPFC of mice, thereby eliciting chronic psychobiological stress responses. |
