Autonomic C1 neurons promote anxiety via activation of vlPAG

Anxiety is an emotional state triggered by the anticipation of a threat. While acute anxiety favors survival by increasing preparedness against future danger, anxiety disorders impair health and negatively impact quality of life. Despite extensive research, the etiology of anxiety disorders remains unresolved, limiting the improvement of therapeutic strategies to alleviate anxiety-related symptoms with increased specificity and efficacy. Here, we applied intersectional tools to elucidate that activation of a small population of autonomic adrenergic neurons in the brainstem, named C1 cells, promotes anxiety-related behaviors. Calcium-based imaging revealed that these cells are activated in stressful situations, while inhibition of C1 neurons reduced fear responses and prevented enhancement of anxiety. These findings implicate C1 neurons as a key brain-body hub for the promotion of anxiety-related behaviors and suggest that targeted inhibition of this circuit could be therapeutically advantageous.