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：
8183950
负责人：
RICHARD D RABBITT
金额：
$ 35.05万
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/8183950
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. PUBLIC HEALTH RELEVANCE: Our results show that pulsed infrared radiation (IR) applied to inner-ear sensory hair-cell epithelia can be used to control the timing and rate of afferent nerve action potentials. If IR excitability has primary origins in hair-cell mitochondrial Ca2+ currents, as indicated by our data, the stimulus would have potential for high impact as a basic science tool, and would offer opportunities for development of new types of therapeutics and neural interfaces.

描述（由申请人提供）：我们最近显示，脉冲红外辐射（IR）应用于体内的半圆形管Crista ampullaris，引起一阶传入神经元的戏剧性和高度可控的反应。许多传入的相位锁定到刺激上，并为每个IR脉冲发射动作潜力。这允许使用IR刺激来控制第八神经传递到大脑的时机和作用速率。即使在长期刺激下，细胞反应也是可靠的。我们使用心肌细胞的体外数据表明，IR通过Uniporter和Na+/Ca2+交换器唤起线粒体Ca2+通量。不知道线粒体IR兴奋性是否也构成了发胶感觉上皮对IR的精致敏感性，或者是否有其他一些机制正在发挥作用。 IR作用的机制将通过检查4个特定目标来确定。我们将1）在广泛的参数空间中建立脉冲IR和热量的剂量反应函数，2）量化细胞电生理学和[Ca2+]对IR的反应，3）记录在IR诱发的传入神经末端的突触后电位和电流的记录。细胞和4）检查IR兴奋性的线粒体成分。预计结果将确定毛细胞中IR光敏性的基本机制。知道该机制将对基础科学的脉冲IR如何使用（例如，唤起线粒体Ca2+瞬变与膜去极化电流）有直接影响。结果还可能对利用IR作用机制的新型IR治疗干预措施和假肢设备的开发产生重大影响。公共卫生相关性：我们的结果表明，适用于内耳感觉发胶上皮的脉冲红外辐射（IR）可用于控制传入的神经动作电位的时间和速率。如我们的数据所示，如果IR兴奋性在线粒体CA2+电流中具有主要起源，那么刺激将具有高影响力作为基础科学工具的潜力，并将为开发新型的治疗疗法和神经界面提供机会。