Pulsed infrared excitability of inner ear: molecular mechanisms and therapeutics

内耳脉冲红外兴奋性：分子机制和治疗

基本信息

批准号：
9014537
负责人：
Suhrud M. Rajguru
金额：
$ 37.47万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2020-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9014537
关键词：
Action Potentials Acute Afferent Neurons Animals Basic Science Cell membrane Cells Characteristics Chemicals Cochlear Implants Data Dependence Development Dose Ear Endoplasmic Reticulum Epithelium Equilibrium Event Eye Movements Fluorescent Probes Future Gentamicins Goals Hair Cells Harvest Health Image Implant Individual Infrared Rays Kinetics Knowledge Label Labyrinth Lasers Lateral Lead Mammals Measures Membrane Potentials Mitochondria Modification Molecular Neonatal Nerve Neurons Neurosciences Neurotransmitters Opsanus Optics Organelles Oxygen Pain Patch-Clamp Techniques Pathology Patients Pattern Physiologic pulse Physiological Play Rattus Receptor Signaling Research Research Project Grants Role Semicircular canal structure Sensory Shapes Signal Pathway Signal Transduction Site Source Speed Stimulus Synapses Synaptic Transmission Techniques Testing Therapeutic Time Tinnitus Tissues Utricle structure Vestibular ganglion Vestibular loss afferent nerve base cell type extracellular ganglion cell genetic manipulation hearing impairment in vivo knock-down mitochondrial membrane neural stimulation neuroepithelium neuronal excitability neuroprosthesis novel postsynaptic radiation response regional difference relating to nervous system research study response spiral ganglion tool uptake

项目摘要

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.

描述（由申请人提供）：我们已经证明，脉冲红外辐射（IR）利用内耳细胞的内源敏感性，并且不需要对细胞进行药理学或遗传操作，从而使大鼠新生前庭和螺旋神经节神经元对细胞内[Ca]作出反应。 ]i 瞬变可能被 2+ 红外脉冲夹带，药理学数据进一步表明 IR 可能激活内质网 Ca2+ 释放，并且强烈依赖于。线粒体 Ca2+ 循环，即使在无 Ca2+ 的细胞外溶液中，反应也持续存在。我们将检查 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+ 储存的功能作用的重要新信息。 IR。这种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制可以激发或抑制单个神经元的活动，无需化学修饰，可以提供即时的高信号。阐明细胞内 Ca2+ 在内耳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。我们还将开发用于局部刺激内耳毛细胞和病理学的新光学探针。最后，我们将在体内检查红外线引起的前庭眼球运动和肌原性反应，并将探索对未来神经假体应用有效且安全的激光参数，这些结果将导致红外线光学刺激的新应用。这种光刺激技术将极大地增强内耳领域的研究，并可能在神经科学领域拥有广泛的应用。