From Physiology to Psychiatry: Key Role of Vagal Interoceptive Pathways in Emotional Control.

Interoception is the awareness of bodily sensations, conveyed by both hormonal and neural signals. The vagus nerve (VN), responsible for transmitting information from peripheral organs to the brain, is the primary neural interoceptive conduit. It is widely accepted that vagal signals are essential for purely physiological functions such as blood pressure maintenance and nutrient intake homeostasis. However, a growing body of evidence, which has taken advantage of new technological advances, suggests that the VN also orchestrates or tunes emotions. Disruption of vagal interoceptive feedback prevents normal emotional control in rodents. Importantly, accumulating evidence indicates that pathological disruption of vagal afferent signals also occurs in humans and may constitute an important risk factor for emotional disorders. Therefore, alleviating vagal interoceptive deficits may constitute a new therapeutic avenue for neurotic and affective disorders. Considering the technical and safety challenges for direct stimulation of brain regions relevant to emotionality disorders, the VN offers a safer and more practical route to potentially achieving similar outcomes. Here, we will highlight the earliest studies that examined the consequences of manipulations of the vagal afferent neurons on anxiety, fear, and mood and integrate these older findings with new research investigating the necessity of vagal afferent neurons in mediating the anxiety- or mood-altering effects of physiological signals. We will also discuss the evolutionary significance of vagal control over emotional states within the boundaries of normal physiology and conclude by discussing the challenges of engaging the vagal interoception as novel therapeutics in mental health disorders.