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：
8303231
负责人：
RICHARD D RABBITT
金额：
$ 32.48万
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 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8303231
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）：我们最近表明，施加到体内半规管壶腹嵴的脉冲红外辐射（IR）会引起一级传入神经元的剧烈且高度可控的反应。许多传入信号锁相刺激，并为每个红外脉冲激发动作电位。这使得红外刺激可用于控制第八神经传输到大脑的动作电位的时间和速率。即使在长期刺激下，细胞反应也很强劲。我们使用心肌细胞的体外数据表明，IR 通过单向转运蛋白和 Na+/Ca2+ 交换器引起线粒体 Ca2+ 通量。目前尚不清楚线粒体红外兴奋性是否也是毛细胞感觉上皮对红外的敏感性的基础，或者是否有其他机制在起作用。 IR 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量的剂量反应函数，2) 量化细胞电生理和对红外的 [Ca2+] 响应，3) 记录应用于头发的红外引起的传入神经末梢的突触后电位和电流细胞，4) 检查 IR 兴奋性的线粒体成分。预计结果将确定毛细胞中红外光敏性的基本机制。了解该机制将对脉冲红外如何用于基础科学产生直接影响（例如诱发线粒体 Ca2+ 瞬变与膜去极化电流）。研究结果还可能对利用红外线作用机制的新型红外线治疗干预措施和假肢装置的开发产生重大影响。