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 Dr. Liberles' lab identified novel olfactory receptor families (TAARs, FPRs), opening up new avenues of research to probe the neuronal basis of perception and behavior. They discovered ligands for many TAARs, including ethological odors derived from carnivores, male mice, and carrion that evoke innate aversion or attraction responses. They 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, their work provides a molecular framework for understanding how sensory inputs are processed to evoke variable and complex behaviors. Recently, Dr. Liberles' lab began exploring internal sensory systems of the vagus nerve, a major conduit between body and brain that controls autonomic physiology. Vagal sensory mechanisms are largely unresolved and present tremendously important problems in sensory biology. They used a molecular approach to deconstruct the vagus nerve, identifying novel receptors and classifying principal cell types. They then generated ires-Cre knock-in mice and adapted genetic tools for anatomical mapping, in vivo imaging, and optogenetic control of vagal neuron subtypes. These approaches revealed sensory neurons that innervate the lung and control breathing, and others that innervate the gastrointestinal tract and control digestion. In a collaborative effort, they also identified a critical role for Piezo mechanoreceptors in the detection of airway stretch and neuronal sensation of blood pressure underlying the baroreceptor reflex. Identifying neurons and receptors that control autonomic physiology builds an essential foundation for mechanistic study and therapy design.