Sensory Encoding in Hair Cells of the Zebrafish Lateral Line

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The process by which the auditory system encodes low-frequency sounds such as those produced by the human voice and a grand piano is not entirely understood. Our long-term goal is to determine how hair cell sensory receptors encode stimulus features into representative sequences of electrical activity in sensory afferent neurons. Understanding this process relies on understanding how intrinsic hair-cell mechanisms contribute to encoded activity. The overall objective of this proposal is to examine sensory encoding in the lateral line system of larval zebrafish. Specifically, the central hypothesis of this proposal is that lateral-line hair cells encode stimulus intensity and duration within defined temporal patterns of afferent activity. The hypothesis was formulated through preliminary experiments on both wild type and transgenic larvae with hair-cell expression of the optogenetic protein, channelrhodhopsin-2 (ChR2), which allows for optical stimulation of hair cells instead of via activation of MET channels with mechanical stimuli. The central hypothesis will be tested with the following two specific aims: 1) Determine the relationship between stimulus features and activity parameters, which include the onset of activity, total amount of activity and the temporal patterns of the activity in wild type larvae; and 2) Compare neuron activity parameters between mechanical and optical stimulation of hair cells in transgenic larvae. Aim 1 will examine the dependence of activity parameters during manipulation of stimulus intensity, duration, and repetition. Experiments in Aim 2 will compare mechanically and optically evoked activity in two different transgenic zebrafish lines that combine optogenetics with wild type data to provide insight into the contribution of intrinsic hair-cell mechanisms on the parameters of afferent neuron activity. The rationale for this proposal is that examination of the relationship between input stimulus features and output activity parameters will further our understanding of auditory perception. The approach is innovative as it utilizes an in vivo approach with electrophysiology on single afferent neurons together with optogenetics to investigate low-frequency encoding in an intact larval zebrafish. Given the importance of low frequency auditory information, and that hair cells are remarkably conserved across vertebrates, our findings will be significant for understanding the function of the mammalian auditory system and will have a positive impact on the treatment of deafness and communication disorders, including the development of cochlear implants that can reliably encode low-frequency information.