Neural processing of auditory and vestibular information plays a crucial role in healthy human communication and balance. This process starts when hair cells transform a mechanical stimulus into a biological signal, and continues as the signal is subsequently transmitted to downstream neural components. We know comparatively little about how information is processed at the next level after hair cells;the primary afferent neurons. This proposal focuses on understanding the relationships among morphology, connectivity, physiology, and development in hair cell afferent neurons. A comprehensive understanding of organization and function is challenging in mammalian afferents due to their inaccessibility and sheer numbers of neurons. In contrast, functional organization of afferents is relatively straightforward to analyze in tractable systems where cell morphology can be visualized in vivo, like the zebrafish lateral line. Zebrafish have quickly established a powerful presence as a model genetic system, which, when combined with their transparency at the larval stage, allows direct observation of afferent connectivity and physiology. Zebrafish display key features of vertebrate hearing and balance circuits, showing similar afferent subtypes and patterns of hair cell connectivity. The goal of the experiments proposed here is to provide an unprecedented, detailed characterization of afferent neurons to understand their role in signal processing more broadly in vertebrate hair cell systems. The intrinsic membrane properties of afferents may be directly related to their somata size or number of hair cells that they contact. This does not seem to be entirely related to their developmental stage, as we have data that suggests that physiology of different cell types is established early on and preserved throughout growth. Furthermore, we will test whether the system is redundantly designed, or has substantial compensatory mechanisms in place, by removing afferent neurons to see their effect on stereotyped motor responses. Without detailed knowledge about how we process information downstream of hair cells we cannot make continued progress towards diagnosing auditory and balance disorders, which have devastating social and health consequences for millions of Americans worldwide.
Healthy hearing and balance depends critically on the normal processing of information received by hair cells in our inner ear. Hair cells directly contact afferent neurons, which provide the first site for potential signal integration. We will provide the first comprehensive analysis of afferent neurons with the goal of understanding how the neural code is shaped by components of the auditory and vestibular pathway that are downstream of hair cell receptors. Understanding the basic biology of how normal hair cell systems function is essential for continued progress towards diagnosing and treating hearing and balance disorders, which have devastating social and health consequences for millions of Americans worldwide.
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