NB-CNS Seminar - Vinny Augustine

Abstract:

Visceral sensory pathways mediate homeostatic reflexes, dysfunction of which leads to many neurological disorders. In this talk, I will highlight the neural basis of the Bezold-Jarisch reflex (BJR) and its association with fainting. The BJR first described in 1867 is a cardioinhibitory reflex speculated to be mediated by vagal sensory neurons (VSNs). We leveraged single-cell RNA sequencing data and HYBRiD tissue clearing and found that neuropeptide Y receptor Y2 (NPY2R) expressing vagal sensory neurons (VSNs) predominately connect the heart ventricular wall to the area postrema (AP). Optogenetic activation of NPY2R VSNs elicits the classic triad of BJR responses- hypotension, bradycardia and suppressed respiration and further causes an animal to faint. Photostimulation during high-resolution echocardiography, and laser doppler flowmetry with behavioral observation, revealed a panoply of phenotypes reflected in clinical syncope, including reduced cardiac output, cerebral hypoperfusion, pupil dilation, and eye-roll. Large scale Neuropixels brain recordings and machine learning-based modeling showed that this manipulation causes suppression of activity across a large distributed neuronal population. Combined, this will be the first demonstration of a genetically defined cardiac reflex, which recapitulates characteristics of human fainting at physiological, behavioral, and neural network levels.