Internal and external senses

Olfaction is one of our five basic external senses, and a principal mechanism by which we perceive the external world. Sensory receptors define our capacity for perception, and we identified novel olfactory receptor families (TAARs, FPRs), opening up new avenues of research to probe the neuronal basis of perception and behavior. We discovered ligands for many TAARs, including ethological odors derived from carnivores, male mice, and carrion that evoke innate aversion or attraction responses. We also identified a pheromone of juvenile mice that inhibits adult sexual behavior, and uncovered a noncanonical mechanism for sweet taste detection in hummingbirds that involved transformation of the ancestral umami receptor. Together, our work provides a molecular framework for understanding how sensory inputs are processed to evoke variable and complex behaviors.

Most of my lab now studies internal sensory systems of the vagus nerve. The vagus nerve contains a diversity of sensory neurons that detect peripheral stimuli such as blood pressure changes at the aortic arch, lung expansion during breathing, meal-induced stomach distension, and chemotherapeutics that induce nausea. Underlying vagal sensory mechanisms are largely unresolved at a molecular level, presenting tremendously important problems in sensory biology. We used a molecular approach to deconstruct the sensory vagus nerve, identifying novel cell surface receptors and classifying a tremendous diversity of cell types. We then generated a large collection of ires-Cre knock-in mice to target each neuron type, and adapted genetic tools for Cre-based anatomical mapping, in vivo imaging, and optogenetic control of vagal neuron activity. We charted various sensory neuron types that innervate the lung and exert powerful effects on breathing, others that monitor and control the digestive system, and yet others that innervate the cardiovascular system or larynx. Together with Ardem Patapoutian, we also identified a critical role for Piezo mechanoreceptors in the sensation of airway stretch, which underlies a classical respiratory reflex termed the Hering-Breuer inspiratory reflex, as well as in the neuronal sensation of blood pressure and the baroreceptor reflex.