CLAUSTRUM ENSEMBLES MEDIATE SOCIAL DEFEAT STRESS-INDUCED HYPERVIGILANCE

Hypervigilance is a core symptom of stress-related psychiatric disorders, yet its underlying mechanisms remain elusive. The claustrum (CLA) is hypothesized to function as a hub for vigilance and attention. Recently, we identified carbonic anhydrase-12 (Car12) as a molecular marker for stress-responsive CLA neurons. However, whether CLA^Car12+ neurons encode vigilance-related behaviors or mediate their stress-induced alterations remains unknown. To address this, we performed calcium imaging in freely moving mice, integrated with anatomical tracing and optogenetic manipulation. We found that CLA^Car12+ ensembles showed heightened activity during social vigilance-like behaviors in the social interaction test. Following 5 consecutive days of social defeat stress, these neurons exhibited significantly enhanced activity during vigilance-like behaviors compared to non-stressed controls. Anterograde tracing revealed that CLA^Car12+ neurons project to the anterior cingulate cortex and insular cortices, key nodes of the salience network. Furthermore, optogenetic activation of CLA^Car12+ neurons induced avoidance-like behaviors, mimicking stress-induced behavioral changes. These findings suggest that CLA^Car12+ neurons act as a critical hub linking stress exposure to negatively biased attention through salience network modulation, providing mechanistic insights into the occurrence of stress-induced hypervigilance.