Abstract
The development of new diagnostics, therapeutics, and treatment paradigms for neurological disorders requires a detailed physiological, cellular, and molecular characterization of the nervous system. Recently, the development of optical techniques for neural imaging and stimulation has led to new insights and become a mainstay in neuroscience. Among the various methods developed, infrared neural stimulation has emerged as a safe, effective, and less invasive approach. In particular, the endogenous mechanisms underlying the response to pulsed infrared radiation offers new opportunities for research. As its applications expand, it is important to characterize the biophysical mechanisms and the molecular processes underlying IR– evoked responses. Here, in a model sensory system, we investigated the physiological eye movement responses evoked by infrared stimulation of the vestibular neuroepithelium and characterized the cellular and molecular mechanisms underlying the photothermal response. We further show that direct infrared stimulation can be a tool to investigate the unique functional morphology of the vestibular system. The results shown in this work indicate that the infrared–induced photothermal responses rely on intracellular calcium activity mediated by the thermosensitive ion channels TRPV4. We further provide evidence suggesting that the level of photosensitivity to infrared radiation varies between cellular elements of the sensory epithelium of vestibular endorgans. However, the IR-evoked activation of the VOR pathway relies on the interaction between pre and post synaptic elements. Finally, we provide evidence supporting the use of focal and multi-point infrared radiation to investigate functional differences between cellular subtypes and regions within the neuroepithelium of the otolith end organs. Overall, the work presented in this thesis reveals new findings of the sensory vestibular neuroepithelium that may prove to be essential for diagnostic and neuroprosthetic devices to treat balance-related disorders.