Abstract
Light at infrared wavelengths has been demonstrated to modulate the pattern of neural signals transmitted from the angular motion sensing semicircular canals of the vestibular system to the brain. In the present study, we have characterized physiological eye movements evoked by focused, pulsed infrared radiation (IR) stimuli directed at an individual semicircular canal in a mammalian model. Pulsed IR (1863 nm) trains were directed at the posterior semicircular canal in a rat using 200–400 µm optical fibers. Evoked bilateral eye movements were measured using a custom-modified video-oculography system. The activation of vestibulo–ocular motor pathways by frequency modulated pulsed IR directed at single posterior semicircular canals evoked significant, characteristic bilateral eye movements. In this case, the resulting eye movements were disconjugate with ipsilateral eye moving upwards with a rotation towards the stimulated ear and the contralateral eye moving downwards. The eye movements were stable through several hours of repeated stimulation and could be maintained with 30 + minutes of continuous, frequency-modulated IR stimulation. Following the measurements, the distance of the fiber from target structures and orientation of the beam relative to vestibular structures were determined using micro-computed tomography. Results highlight the spatial selectivity of optical stimulation. Our results demonstrate a novel strategy for direct optical stimulation of the vestibular pathway in rodents and lays the groundwork for future applications of optical neural stimulation in inner ear research and therapeutic applications.
Similar content being viewed by others
References
Barrett, J. N., et al. Pulsed infrared releases Ca2+ from the endoplasmic reticulum of cultured spiral ganglion neurons. J. Neurophysiol. 2018. https://doi.org/10.1152/jn.00740.2017.
Bec, J. M., et al. Characteristics of laser stimulation by near infrared pulses of retinal and vestibular primary neurons. Lasers Surg. Med. 44(9):736–745, 2012.
Bernstein, J. G., P. A. Garrity, and E. S. Boyden. Optogenetics and thermogenetics: technologies for controlling the activity of targeted cells within intact neural circuits. Curr. Opin. Neurobiol. 22(1):61–71, 2012.
Boyden, E. S., et al. Millisecond-timescale, genetically targeted optical control of neural activity. Nat. Neurosci. 8(9):1263–1268, 2005.
Cayce, J. M., et al. Calcium imaging of infrared-stimulated activity in rodent brain. Cell Calcium 55(4):183–190, 2014.
Cohen, B., and J. I. Suzuki. Eye movements induced by ampullary nerve stimulation. Am. J. Physiol. 204:347–351, 1963.
Cohen, B., J. I. Suzuki, and M. B. Bender. Eye movements from semicircular canal nerve stimulation in the cat. Ann. Otol. Rhinol. Laryngol. 73:153–169, 1964.
Cohen, B., et al. Spatial orientation of the angular vestibulo–ocular reflex. J. Vestib. Res. 9(3):163–172, 1999.
Curthoys, I. S. Eye movements produced by utricular and saccular stimulation. Aviat. Space Environ. Med. 58(9 Pt 2):A192–A197, 1987.
Dai, C., et al. Restoration of 3D vestibular sensation in rhesus monkeys using a multichannel vestibular prosthesis. Hear. Res. 281(1–2):74–83, 2011.
Deisseroth, K., and M. J. Schnitzer. Engineering approaches to illuminating brain structure and dynamics. Neuron 80(3):568–577, 2013.
Dellepiane, M., R. Mora, and A. Salami. Vestibular and optokinetic nystagmus in ketamine-anesthetized rabbits. Int. Tinnitus J. 13(1):15, 2007.
Dittami, G. M., et al. Intracellular calcium transients evoked by pulsed infrared radiation in neonatal cardiomyocytes. J. Physiol. 589(6):1295–1306, 2011.
Fenno, L., O. Yizhar, and K. Deisseroth. The development and application of optogenetics. Annu. Rev. Neurosci. 34:389–412, 2011.
Fluur, E. Influences of semicircular ducts on extraocular muscles. Acta Otolaryngol. Suppl. 149:1–46, 1959.
Fluur, E., and A. Mellstrom. Saccular stimulation and oculomotor reactions. Laryngoscope 80(11):1713–1721, 1970.
Fridman, G. Y., et al. Vestibulo–ocular reflex responses to a multichannel vestibular prosthesis incorporating a 3D coordinate transformation for correction of misalignment. J. Assoc. Res. Otolaryngol. 11(3):367–381, 2010.
Fried, N. M., et al. Noncontact stimulation of the cavernous nerves in the rat prostate using a tunable-wavelength thulium fiber laser. J. Endourol. 22(3):409–414, 2008.
Hale, G. M., and M. R. Querry. Optical constants of water in the 200 nm to 200 µm region. Appl. Opt. 12:555–563, 1973.
Harris, D.M., et al. Optical nerve stimulation for a vestibular prosthesis. In: Proceedings of SPIE 7180, 2009.
Hernandez, V. H., et al. Optogenetic stimulation of the auditory pathway. J. Clin. Invest. 124(3):1114–1129, 2014.
Izzo, A. D., et al. Laser stimulation of the auditory nerve. Lasers Surg. Med. 38(8):745–753, 2006.
Jenkins, M. W., et al. Optical pacing of the embryonic heart. Nat. Photon. 4(9):623–626, 2010.
Katz, E. J., et al. Excitation of primary afferent neurons by near-infrared light in vitro. Neuroreport 21(9):662–666, 2010.
Kawashima, Y., et al. Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes. J. Clin. Invest. 121(12):4796–4809, 2011.
Lewis, R. F., et al. Spatial and temporal properties of eye movements produced by electrical stimulation of semicircular canal afferents. J. Neurophysiol. 108(5):1511–1520, 2012.
Merfeld, D. M., F. O. Black, and S. Wade. Clinical use of three-dimensional video measurements of eye movements. Otolaryngol. Head Neck Surg. 118(3 Pt 2):S35–S38, 1998.
Mettens, P., E. Godaux, and G. Chéron. Effects of ketamine on ocular movements of the cat. J. Vestib. Res. 1:325–338, 1991.
Minor, L. B. Gentamicin-induced bilateral vestibular hypofunction. JAMA 279(7):541–544, 1998.
Moreau, D., et al. Infrared neural stimulation induces intracellular Ca2+ release mediated by phospholipase C. J. Biophoton. 11:e201700020, 2017.
Moreno, L. E., et al. Infrared neural stimulation: beam path in the guinea pig cochlea. Hear. Res. 282(1–2):289–302, 2011.
Nair, G., et al. Effects of common anesthetics on eye movement and electroretinogram. Doc. Ophthalmol. 122(3):163–176, 2011.
Pan, B., et al. TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of the mammalian inner ear. Neuron 79(3):504–515, 2013.
Poon, C. C., and M. G. Irwin. Anaesthesia for deep brain stimulation and in patients with implanted neurostimulator devices. Br. J. Anaesth. 103(2):152–165, 2009.
Rabbitt, R. D., et al. Heat pulse excitability of vestibular hair cells and afferent neurons. J. Neurophysiol. 116(2):825–843, 2016.
Rahman, M. A., et al. Restoring the 3D vestibulo–ocular reflex via electrical stimulation: the Johns Hopkins multichannel vestibular prosthesis project. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2011:3142–3145, 2011.
Rajguru, S. M., et al. Infrared photostimulation of the Crista Ampullaris. J. Physiol. 589(6):1283–1294, 2011.
Rajguru, S. M., et al. Infrared photostimulation of the Crista Ampullaris. J. Physiol. 589(Pt 6):1283–1294, 2011.
Raphan, T., V. Matsuo, and B. Cohen. Velocity storage in the vestibulo–ocular reflex arc (VOR). Exp. Brain Res. 35(2):229–248, 1979.
Rein, M. L., and J. M. Deussing. The optogenetic (r)evolution. Mol. Genet. Genom. 287(2):95–109, 2012.
Richter, C. P., and X. Tan. Photons and neurons. Hear. Res. 311:72–88, 2014.
Simpson, J. I., and W. Graf. Eye-muscle geometry and compensatory eye movements in lateral-eyed and frontal-eyed animals. Ann. N. Y. Acad. Sci. 374:20–30, 1981.
Smith, N. I., et al. A femtosecond laser pacemaker for heart muscle cells. Opt. Expr. 16(12):8604–8616, 2008.
Stahl, J. S., A. M. van Alphen, and C. I. De Zeeuw. A comparison of video and magnetic search coil recordings of mouse eye movements. J. Neurosci. Methods 99(1–2):101–110, 2000.
Suzuki, J. I. Vestibular and spinal control of eye movements. Bibl. Ophthalmol. 82:109–115, 1972.
Suzuki, J. I., and B. Cohen. Head, eye, body and limb movements from semicircular canal nerves. Exp. Neurol. 10:393–405, 1964.
Suzuki, J. I., B. Cohen, and M. B. Bender. Compensatory eye movements induced by vertical semicircular canal stimulation. Exp. Neurol. 9:137–160, 1964.
Suzuki, J. I., K. Tokumasu, and K. Goto. Eye movements from single utricular nerve stimulation in the cat. Acta Otolaryngol. 68(4):350–362, 1969.
Tan, X., et al. Auditory neural activity in congenitally deaf mice induced by infrared neural stimulation. Sci. Rep. 8(1):388, 2018.
Teudt, I. U., et al. Optical stimulation of the facial nerve: a new monitoring technique? Laryngoscope 117(9):1641–1647, 2007.
Tian, L., et al. Short-wavelength infrared laser activates the auditory neurons: comparing the effect of 980 vs. 810 nm wavelength. Lasers Med. Sci. 32(2):357–362, 2017.
van de Berg, R., et al. The modified ampullar approach for vestibular implant surgery: feasibility and its first application in a human with a long-term vestibular loss. Front Neurol. 3:18, 2012.
Walsh, A. J., et al. Action potential block in neurons by infrared light. Neurophotonics 3(4):040501, 2016.
Wells, J., et al. Application of infrared light for in vivo neural stimulation. J. Biomed. Opt. 10(6):064003, 2005.
Acknowledgments
The authors sincerely thank Dr. Gaëtan Delcroix for his technical help and the GRECC Lab at the Miami VA Medical Center for generously giving us access to the MicroCT scanner.
Conflict of interest
The authors declare no competing financial interests.
Funding
This work was supported by R01DC013798 (SMR).
Author information
Authors and Affiliations
Corresponding author
Additional information
Associate Editor Leonidas D. Iasemidis oversaw the review of this article.
Rights and permissions
About this article
Cite this article
Jiang, W., Rajguru, S.M. Eye Movements Evoked by Pulsed Infrared Radiation of the Rat Vestibular System. Ann Biomed Eng 46, 1406–1418 (2018). https://doi.org/10.1007/s10439-018-2059-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10439-018-2059-x