Interoceptive network that co-regulates emotional and autonomic responses

About This Grant

Our autonomic regulation of respiration, digestion, circulation, and immune functions is closely coupled with emotional states. Anxiety elevates blood pressure, stress induces sighing, and anger suppresses digestion, while slow breathing promotes calmness. Despite these well-documented phenomena, the neural mechanisms underlying the tight coupling between emotion and autonomic control remain poorly understood, limiting the development of complementary therapies for emotional disorders, such as anxiety, phobia, and depression, and autonomic disorders, including hypertension, diabetes, gastroparesis, tachycardia, pulmonary diseases, sleep apnea, and many others. The interoceptive system continuously monitors visceral organ status. Many bodily cues are transmitted via the vagus nerve to the nucleus of the solitary tract (NTS) in the brainstem, the primary sensory gateway for interoception. The NTS processes interoceptive information and distributes it, via its ascending pathways, to multiple brain regions, including autonomic motor nuclei, the hypothalamus, and limbic structures, to orchestrate coordinated whole-body autonomic, emotional, and behavioral responses. The goal of this proposal is to pinpoint the neural substrate that mediate bodily signal-evoked emotional and autonomic responses respectively. Using viral-genetic tracing, our preliminary study shows that single NTS neurons extend highly collateral projections to multiple targets. In particular, we identified a group of NTS neurons that jointly innervate brain regions implicated in aversion/anxiety and autonomic control. This previously uncharacterized ascending interoceptive pathway forms the basis of our hypothesis that axonal collaterals from the same neurons jointly regulate autonomic and emotional responses. Using a portfolio of genetic tools that enable us to precisely record and manipulate genetically defined NTS pathways, we will, through three specific aims, determine the anatomical signatures that underlie the tightly associated emotional and autonomic responses. The completion of this proposal will help establish an anatomical-functional blueprint of ascending brainstem interoceptive circuits, laying the foundation for future investigations. By revealing the multisystem interactions of the interoceptive network, this proposal will provide insight into how complementary approaches, such as meditation and breathing-based therapies, holistically improve autonomic emotional well-being.