Pulsed infrared excitability of inner ear: molecular mechanisms and therapeutics

 描述(申请人提供)：我们已经证明，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物或遗传操作。新生大鼠前庭神经细胞和螺旋神经节神经元通过胞内[Ca]i瞬变反应，这种瞬变可被2+红外脉冲所携带。药理学数据进一步表明，IR可能激活内质网钙释放，并强烈依赖于线粒体的钙循环，即使在无钙的胞外溶液中，这种反应也持续存在。我们将检测内质网和线粒体对脉冲IR的反应。这些结果将为IR神经元的兴奋性和细胞内关键的钙储存在IR效应中的功能作用提供重要的新信息。这一知识将适用于各种类型的细胞，包括毛细胞和神经元。对细胞内细胞器和信号通路的精确光控制可以在不需要化学修饰的情况下刺激或抑制单个神经元的活动，这可能在神经科学中提供立即的高影响应用。阐明细胞内钙离子在内耳突触传递中的作用将为理解其在维持生理功能中的作用和在病理学中的作用奠定基础。我们还将开发新的光学探针，用于对内耳毛细胞和神经元进行局部刺激。最后，我们将在活体内检测IR诱发的前庭眼球运动和肌源性反应，并将为未来的神经假体应用探索有效和安全的激光参数(S)。这一结果将导致红外光学刺激在基础科学中的新应用，并可能使患有前庭损失、听力损失、耳鸣和疼痛的患者受益。这种光刺激技术将极大地促进内耳领域的研究，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.