Research

We study the neural circuits, physiological mechanisms and neuroimmune pathways by which the nervous system senses and regulates immune and metabolic processes and cardiopulmonary functions. To answer these fundamental questions, we have developed implants for chronic stimulation and chronic recording of the vagus nerve in anesthetized and freely moving mice and characterized the chronic cardiopulmonary effects of VNS in rats. We found that stimulation of the vagus and abdominal autonomic nerves elicits transient release of norepinephrine in the spleen, producing anti-inflammatory effects via splenic macrophages. In response to the release of NE in the speen, VNS also modulates B-cell function and antibody production, through specific noradrenergic and cholinergic receptors on immune cells, in a stimulation schedule-dependent manner. Stimulation of the sensory innervation of the liver normalizes glucose homeostasis in animal models of diabetes.

As VNS increases its therapeutic footprint, there is need for more organ- and function-selective devices that target mechanisms specific to the affected organ(s), often delivered in closed-loop mode. We have developed methods to quantify VNS-engagement of fibers regulating cardiopulmonary functions, and showed that stimulus polarity and kHz-frequency stimuli selectively activate vagal fibers. Recently, we characterized the microscopic, functional anatomy of the vagus nerve in swine and developed a multi-contact electrode and method for fascicular VNS. We also showed interferential VNS through a multi-contact electrode modulates specific vagal fibers in a precise, temporally and spatially, manner.

We study neuroimmune dysfunction and test neuroimmune modulation therapies in cardiovascular diseases with an inflammatory component, such as pulmonary hypertension, heart failure and cardiac arrhythmias. We are particularly interested in the use of focused ultrasound neuromodulation targeting neural circuits to suppress inflammation in humans and in animal models of diseases like pulmonary hypertension, and neuropathic pain.