Lumbreras Vicente, Bas Esperanza, Gupta Chhavi, Rajguru Suhrud M
Department of Biomedical Engineering, University of Miami, Miami, Florida; and.
Department of Otolaryngology, University of Miami, Miami, Florida.
J Neurophysiol. 2014 Sep 15;112(6):1246-55. doi: 10.1152/jn.00253.2014. Epub 2014 Jun 11.
Cochlear implants are currently the most effective solution for profound sensorineural hearing loss, and vestibular prostheses are under development to treat bilateral vestibulopathies. Electrical current spread in these neuroprostheses limits channel independence and, in some cases, may impair their performance. In comparison, optical stimuli that are spatially confined may result in a significant functional improvement. Pulsed infrared radiation (IR) has previously been shown to elicit responses in neurons. This study analyzes the response of neonatal rat spiral and vestibular ganglion neurons in vitro to IR (wavelength = 1,863 nm) using Ca(2+) imaging. Both types of neurons responded consistently with robust intracellular Ca(2+) ([Ca(2+)]i) transients that matched the low-frequency IR pulses applied (4 ms, 0.25-1 pps). Radiant exposures of ∼637 mJ/cm(2) resulted in continual neuronal activation. Temperature or [Ca(2+)] variations in the media did not alter the IR-evoked transients, ruling out extracellular Ca(2+) involvement or primary mediation by thermal effects on the plasma membrane. While blockage of Na(+), K(+), and Ca(2+) plasma membrane channels did not alter the IR-evoked response, blocking of mitochondrial Ca(2+) cycling with CGP-37157 or ruthenium red reversibly inhibited the IR-evoked [Ca(2+)]i transients. Additionally, the magnitude of the IR-evoked transients was dependent on ryanodine and cyclopiazonic acid-dependent Ca(2+) release. These results suggest that IR modulation of intracellular calcium cycling contributes to stimulation of spiral and vestibular ganglion neurons. As a whole, the results suggest selective excitation of neurons in the IR beam path and the potential of IR stimulation in future auditory and vestibular prostheses.
人工耳蜗是目前治疗重度感音神经性听力损失最有效的解决方案，前庭假体也正在研发中以治疗双侧前庭病变。这些神经假体中的电流扩散限制了通道的独立性，在某些情况下，可能会损害其性能。相比之下，空间受限的光刺激可能会带来显著的功能改善。先前已证明脉冲红外辐射（IR）可引发神经元反应。本研究使用钙成像分析新生大鼠螺旋神经节和前庭神经节神经元在体外对红外光（波长 = 1,863 nm）的反应。两种类型的神经元均一致地产生了强烈的细胞内钙（[Ca²⁺]i）瞬变，与施加的低频红外脉冲（4毫秒，0.25 - 1次/秒）相匹配。约637 mJ/cm²的辐射暴露导致神经元持续激活。培养基中的温度或[Ca²⁺]变化并未改变红外诱发的瞬变，排除了细胞外Ca²⁺参与或热效应作用于质膜的主要介导作用。虽然阻断Na⁺、K⁺和Ca²⁺质膜通道并未改变红外诱发的反应，但用CGP - 37157或钌红阻断线粒体Ca²⁺循环可可逆地抑制红外诱发的[Ca²⁺]i瞬变。此外，红外诱发瞬变的幅度取决于ryanodine和环匹阿尼酸依赖性Ca²⁺释放。这些结果表明，红外对细胞内钙循环的调节有助于刺激螺旋神经节和前庭神经节神经元。总体而言，结果表明对红外光束路径中的神经元有选择性激发作用，以及红外刺激在未来听觉和前庭假体中的潜力。
