Mechanisms of signaling in otoconial organs

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Project summary. Normal behavior and spatial orientation depend upon vestibular signals from the inner ear. There are two major subdivisions of the vestibular periphery: semicircular canals and otoconial organs. The former have been intensively studied. Otoconial organs are much less well understood, even though studies of central vestibular processing increasingly highlight their importance in control of posture, gaze, spatial orientation, and vegetative functions. Thus, there is a pressing need to understand this important subdivision of the labyrinth. We propose to address this need by analyzing the mechanical and biophysical origins of signals from a major otoconial organ, the utricle. Our experimental preparation is a turtle, one of the premier model systems for analyses of peripheral auditory and vestibular mechanisms. This multidisciplinary initiative analyzes utricular mechanisms at levels from behavior to cellular modeling. It builds on results from our current studies of biomechanics, which have yielded the most detailed data base on the structure and mechanics of the utricle available for any vertebrate. Aim 1 uses high-speed video recording and NMR images of the labyrinth to quantify the stimuli that utricular hair cells are exposed to in freely behaving animals. Aim 2 and Aim 3 combine experimental mechanics with biophysical and computational analyses to characterize important mechanical and hair cell responses to these stimuli. Aim 4 uses morphophysiology, information analysis, and modeling to quantify the resulting afferent signals and their information content, contrast these signals with hair cell responses to the same stimuli, and test hypotheses about the origins of signal diversity in utricular afferents. Thus, the proposed research continues our efforts to build the first detailed, quantitative description of the mechanisms that shape utricular signals to the CMS. Relevance. Vestibular dysfunction is a common cause of physician visits. It can be particularly disabling, and vestibular deficits are thus a significant medical, social, and financial concern. In spite of its importance, the vestibular system, and otoconial organs in particular, are far less well understood than other sensory systems. We need new knowledge of otoconial organ function to improve diagnosis and treatment strategies. By contributing to this knowledge, the proposed research is directly relevant to the mission of the NIDCD.