Gap junctions represent an important mode of intercellular communication in the nervous system. Gap junctions allow exchange of small bioactive substances, including second messengers, between coupled cells. They are involved in synchronizing neuronal activity and increasing signal-to-noise ratio of sensory detection in the visual system. In recent studies, we have shown that mature olfactory receptor neurons (ORNs) express gap junction protein subunits connexin 36, connexin 43, and connexin 45. Since ORNs display high input resistance, opening of a single ion channel can elicit action potential generation. Thus, even a few gap junctional channels could substantially alter the electrical properties of ORNs. In addition, one neuron may activate neighboring neurons by passing second messengers via gap junctions. Our demonstration of the expression of gap junctions in mature olfactory receptor neurons raises the question of whether communication through gap junctions has a functional role in peripheral olfactory coding. I hypothesize that coupling between certain olfactory neurons is an important mechanism for maintaining olfactory sensitivity and response intensity to certain odors. The present application is a part of our overall effect to understand the function of gap junctions in olfactory perception. In this application, I propose to study the olfactory responses at basal and at gap junction disrupted conditions, at populational and cellular levels, in in situ preparations. My specific aims are: Aim 1. Perform a functional characterization of cell-cell communication through gap junctions in mature olfactory receptor neurons using the calcium imaging method; and Aim 2. Determine the role of gap junctions in olfactory transduction by pharmacological and genetic disruption of gap junctions in the olfactory epithelium. Electrophysiological, biophysical, and mouse genetic approaches will be used to accomplish the research goals. My study will not only provide information advancing our understanding of peripheral odor coding mechanisms but also on the role of gap junctions in neuronal function.
NIH ExPorter
NIH ExPorter