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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC011481-03
Application #
8490340
Study Section
Auditory System Study Section (AUD)
Program Officer
Cyr, Janet
Project Start
2011-07-19
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
3
Fiscal Year
2013
Total Cost
$308,558
Indirect Cost
$79,633
Name
Marine Biological Laboratory
Department
Type
DUNS #
001933779
City
Woods Hole
State
MA
Country
United States
Zip Code
02543
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Liu, Qiang; Frerck, Micah J; Holman, Holly A et al. (2014) Exciting cell membranes with a blustering heat shock. Biophys J 106:1570-7
Lumbreras, Vicente; Bas, Esperanza; Gupta, Chhavi et al. (2014) Pulsed infrared radiation excites cultured neonatal spiral and vestibular ganglion neurons by modulating mitochondrial calcium cycling. J Neurophysiol 112:1246-55
Shapiro, Mikhail G; Homma, Kazuaki; Villarreal, Sebastian et al. (2012) Infrared light excites cells by changing their electrical capacitance. Nat Commun 3:736