Pulsed infrared radiation excites cultured neonatal spiral and vestibular ganglion neurons by modulating mitochondrial calcium cycling

Abstract

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 Ca2+ imaging. Both types of neurons responded consistently with robust intracellular Ca2+ ([Ca2+]i) transients that matched the low-frequency IR pulses applied (4 ms, 0.25–1 pps). Radiant exposures of ∼637 mJ/cm2 resulted in continual neuronal activation. Temperature or [Ca2+] variations in the media did not alter the IR-evoked transients, ruling out extracellular Ca2+ involvement or primary mediation by thermal effects on the plasma membrane. While blockage of Na+, K+, and Ca2+ plasma membrane channels did not alter the IR-evoked response, blocking of mitochondrial Ca2+ cycling with CGP-37157 or ruthenium red reversibly inhibited the IR-evoked [Ca2+]i transients. Additionally, the magnitude of the IR-evoked transients was dependent on ryanodine and cyclopiazonic acid-dependent Ca2+ 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.