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Infrared Photoactivation of Inner-Ear Hair Cells

内耳毛细胞的红外光激活

基本信息

批准号：
8490340
负责人：
RICHARD D RABBITT
金额：
$ 30.86万
依托单位：
MARINE BIOLOGICAL LABORATORY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-19 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8490340
关键词：
Action Potentials Afferent Neurons Basic Science Brain Buffers Calcium Calorimetry Cardiac Myocytes Cells Crista ampullaris Data Development Dose Effectiveness Epithelium Evoked Potentials Fire - disasters Goals Hair Cells Health Heating Image In Vitro Infrared Rays Labyrinth Lasers Mechanical Stimulation Mechanics Membrane Membrane Potentials Mitochondria Molecular Neonatal Nerve Nerve Endings Optics Organ Phase Photosensitivity Physiologic pulse Physiological Play Prosthesis Radiation Radiation Tolerance Relative (related person)Role Semicircular canal structure Sensory Sensory Hair Signal Transduction Spectrum Analysis Stimulus Synapses Temperature Testing Therapeutic Therapeutic Intervention Time Tissues Vestibular Hair Cells Work absorption afferent nerve in vivo neurotransmitter release patch clamp photoactivation postsynaptic presynaptic relating to nervous system research study response statistics tool uptake voltage voltage clamp

项目摘要

DESCRIPTION (provided by applicant): We have recently shown that pulsed infrared radiation (IR) applied to the semicircular canal crista ampullaris in vivo evokes dramatic and highly controllable responses of first order afferent neurons. Many afferents phase lock to the stimulus and fire an action potential for each IR pulse. This allows IR stimuli to be used to control the timing and rate of action potentials transmitted by the 8th nerve to the brain. The cellular response is robust, even under long-term stimulation. Our in vitro data using cardiomyocytes indicates that IR evokes mitochondrial Ca2+ flux via the uniporter and the Na+/Ca2+ exchanger. It is not know if mitochondrial IR excitability also underlies the exquisite sensitivity of hair-cell sensory epithelia to IR, or if some other mechanism is at play. The mechanism of IR action will be determined through examination of 4 specific aims. We will 1) establish dose-response functions for pulsed IR and heat across a broad parameter space, 2) quantify cellular electrophysiological and [Ca2+] responses to IR, 3) record postsynaptic potentials and currents in afferent nerve endings evoked by IR applied to hair cells, and 4) examine the mitochondrial component of IR excitability. Results are expected to determine the fundamental mechanism of IR photosensitivity in hair cells. Knowing the mechanism will have immediate impact on how pulsed IR is used for basic science (e.g. to evoke mitochondrial Ca2+ transients vs. membrane depolarizing currents). Results also have potential for significant impact on the development of new IR therapeutic interventions and prosthetic devices that take advantage of the mechanism of IR action.

描述（由申请人提供）：我们最近证明，脉冲红外辐射（IR）应用于半规管壶腹嵴在体内唤起了一级传入神经元的戏剧性和高度可控的反应。许多传入相锁定刺激，并为每个红外脉冲发射一个动作电位。这使得红外刺激可以用来控制第8神经向大脑传递动作电位的时间和速率。即使在长期刺激下，细胞的反应也很强烈。我们使用心肌细胞的体外数据表明，IR通过单转运体和Na+/Ca2+交换器唤起线粒体Ca2+通量。目前尚不清楚线粒体IR兴奋性是否也是毛细胞感觉上皮对IR敏感的基础，或者是否有其他机制在起作用。IR的作用机制将通过检查4个具体目标来确定。我们将1)在广泛的参数空间内建立脉冲红外和热的剂量反应函数，2)量化细胞对红外的电生理和[Ca2+]反应，3)记录红外应用于毛细胞引起的传入神经末梢的突触后电位和电流，4)检查红外兴奋性的线粒体成分。研究结果有望确定毛细胞红外光敏性的基本机制。了解其机制将对如何将脉冲红外用于基础科学（例如，唤起线粒体Ca2+瞬态与膜去极化电流）产生直接影响。研究结果还可能对开发新的IR治疗干预措施和利用IR作用机制的假体装置产生重大影响。