Olfactory receptor neurons (ORNs) are located in the olfactory epithelium in the nasal cavity and are the primary neurons that convert odorous information into nerve signals to be conveyed to the brain. As such, they drive a variety of behaviors including food localization, friend and foe recognition, and evaluation of reproductive status. Cilia that emanate from ORNs into the mucus that covers the epithelium are the site of olfactory transduction, and cilia from neighboring ORNs form an entangled mesh. Upon activation by odorants, a cAMP and Ca2+-based transduction cascade generates a ciliary transduction current that depolarizes the ORNs and leads to the generation of Ca2+-driven action potentials in the cell body. But little is known about the Ca2+ kinetics in cilia and the rest of the ORN, or how cilia from different ORNs might interact and influence each other within the environment of the mucus. The goal of this NIDCD Research Career Enhancement Award for Established Investigators proposal is to enhance the applicant?s current research program to learn and adopt cutting-edge lattice light sheet microscopy approaches to monitor Ca2+ responses in ORNs in the intact olfactory epithelium using genetically-encoded Ca2+ indicators. The long-term goal of the proposed mentored research experience is to understand how ORNs function in their polarized environment, how Ca2+ contributes to olfactory signaling and how the interaction of cilia in the mucosal environment contributes to coding and signaling of olfactory information.
Olfactory receptor neurons in the nasal cavity convert odorants into action potentials but have to do so in a changing mucosal environment that is also common to cilia, the sensory organelles that detect odorants, originating from many neurons. Using in situ Ca2+ imaging, the proposed work will address how olfactory receptor neurons code for odorants in the constraints of their epithelial environment. A better understanding of how changes in the nasal cavity impact olfactory receptor neuron function will be an important step towards determining how the sense of smell is altered by various disease states and how this can affect wellbeing.
