Pulsed infrared excitability of inner ear: molecular mechanisms and therapeutics

 描述（由申请人提供）：我们已经表明，脉冲红外辐射（IR）利用内耳细胞的内源性敏感性，不需要对细胞进行药理学或遗传学操作。大鼠新生前庭和螺旋神经节神经元响应细胞内[Ca]i瞬变，可以夹带的2+红外脉冲。药理学数据进一步表明，IR可能激活内质网Ca 2+释放，强烈依赖于线粒体Ca 2+循环，并且即使在无Ca 2+的细胞外溶液中，反应也持续存在。我们将研究ER和线粒体对脉冲IR的反应。结果将提供有关IR神经元兴奋性和关键细胞内Ca2+商店在IR影响中的功能作用的重要新信息。这些知识将适用于各种细胞类型，包括毛细胞和神经元。细胞内细胞器和信号通路的精确光控，具有激发或抑制单个神经元活动的可能性，而无需化学修饰，可以在神经科学中提供即时的高影响力应用。阐明细胞内Ca 2+在内耳突触突触传递中的作用将为理解其在维持生理功能和病理学中的作用奠定基础。我们还将开发新的光学探针，用于内耳毛细胞和神经元的局部刺激。最后，我们将检查体内IR诱发的前庭眼球运动和肌源性反应，并将探索未来神经假体应用的有效和安全的激光参数。这些结果将导致红外光学刺激在基础科学中的新应用，并可能使前庭功能丧失、听力丧失、耳鸣和疼痛的患者受益。这种光学刺激技术将大大加强内耳领域的研究，并可能在神经科学中有广泛的应用。

 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.