Pulsed infrared excitability of inner ear: molecular mechanisms and therapeutics

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 DESCRIPTION (provided by applicant): We have shown that pulsed infrared radiation (IR) utilizes endogenous sensitivity of cells in the inner ear and does not require pharmacological or genetic manipulation of the cells. Rat neonatal vestibular and spiral ganglion neurons responded with intracellular [Ca]i transients that could be entrained by the 2+ infrared pulses. Pharmacological data further show that IR likely activates the endoplasmic reticulum Ca2+ release with strong dependence on mitochondrial Ca2+ cycling, and the responses persist even in Ca2+-free extracellular solution. We will examine responses of ER and mitochondria to pulsed IR. Results will provide significant new information about IR neuronal excitability and functional role of key intracellular Ca2+ stores in the effects of IR. This knowledge will apply across cell types, including hair cells and neurons. The precise photocontrol of intracellular organelles and signaling pathways with the possibility to excite or inhibit individual neuron activity, without chemical modifications, could provide immediate high impact applications in neuroscience. Clarifying the role of intracellular Ca2+ in synaptic transmission in inner ear synapses will lay the groundwork for understanding its role in maintaining physiological function and in pathology. We will also develop new optical probes for localized stimulation of inner ear hair cells and neurons. Finally we will examine IR evoked vestibular eye movement and myogenic responses in vivo and will explore the laser parameters effective and safe for future neuroprosthetic application(s). The results will lead to new applications of IR optical stimuli in basic science and potentially benefit patients suffering from vestibular loss, hearing loss, tinnits and pain. This optical stimulation technique will greatly enhance research in the inner ear field and likely have broad applications in neuroscience.