The broad, long-term objective of this research is to augment our understanding of the brain's ability to encode external information and to heighten our knowledge of the degree of sensory processing that takes place in the peripheral nervous system prior to its receipt at higher brain centers. Second messenger and related transduction cascades are a fundamental feature of electrical signalling, cell communication, and gene expression/regulation not only for cells that process sensory information but virtually for all cells across an array of systems.
The specific aim of this research proposal is to discern the functional mechanism by which chemosignals will trigger an electrical response in the vertebrate vomeronasal receptor cell (VRN) membrane; the physiological basis for sensory transduction in the vomeronasal organ (VNO). Few studies have described the electrophysiological properties of vertebrate VRNs that must transduce chemical signals involved in the universal life processes of food finding, social interaction, and reproduction, and which are ultimately involved in the execution of species-typical behavior sand the initiation of neuroendocrine changes. This proposal will expand upon the body of biophysical properties known for these neurons, and apply single channel recording, whole-cell perfusion of G protein antibodies, and patch-cram recording techniques with biochemical and immunocytochemical verification of the VNO transduction components as a means for delineating the FUNCTIONAL odorant to electrical transduction in the vertebrate vomeronasal olfactory system. The proposal is designed to address: (1) Are there VNO specific stimuli? (2) Are GTP-binding proteins localized to the putative subcellular site of signal transduction? (3) Which GTP-binding proteins are physiologically involved in chemosignal transduction? (4) Can inositol phospholipids or cyclic nucleotides directly gate ion channels in the VNO? and (5) Can chemosignals evoke any second-messenger gated ion channel activity. This combined biophysical/biochemical/immunochemical approach for dissecting the molecular details of VNO transduction should provide new data concerning VNO function, which is currently unknown in humans.
|Mast, Thomas G; Brann, Jessica H; Fadool, Debra A (2010) The TRPC2 channel forms protein-protein interactions with Homer and RTP in the rat vomeronasal organ. BMC Neurosci 11:61|
|Labra, Antonieta; Brann, Jessica H; Fadool, Debra A (2005) Heterogeneity of voltage- and chemosignal-activated response profiles in vomeronasal sensory neurons. J Neurophysiol 94:2535-48|
|Murphy, F A; Tucker, K; Fadool, D A (2001) Sexual dimorphism and developmental expression of signal-transduction machinery in the vomeronasal organ. J Comp Neurol 432:61-74|