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A red thread as a guide in the vestibular labyrinth

2011; Wiley; Volume: 589; Issue: 6 Linguagem: Inglês

10.1113/jphysiol.2011.206763

1469-7793

Ian S. Curthoys,

Connexins and lens biology

Whereas Theseus used Ariadne's red thread as his guide in the labyrinth of Crete after slaying the Minotaur, in this issue of The Journal of Physiology Rajguru et al. (2011) have used a red thread of light from an infrared laser travelling down an optical fibre to guide us to a stunningly bright insight into intracellular events in the vestibular labyrinth of the inner ear. Up to now vestibular hair cell receptors have been stimulated either by mechanical shearing of the cilia relative to the cell body caused by fluid flow in the semicircular canal, or by electrical stimulation. This paper reports an entirely new means of vestibular hair cell stimulation – by light. The authors have shown that photostimulation of the crista of the toadfish semicircular canal by brief (220 μs) pulses of very long wavelength (1852 nm), low power, infrared (IR) laser illumination conveyed by a fine optical fibre to the crista, modulates the firing of primary semicircular canal afferent neurons from that crista. Some afferents were excited, some were inhibited and some showed mixed excitatory/inhibitory responses. Some afferent neurons phase-lock at pulse rates up to 96 pulses s−1. While activation of neurons by optical means has been an area of great recent interest, the paper by Rajguru et al. is, to my knowledge, the first time that optical stimulation has been used to activate vestibular receptors in healthy organisms without any genetic modification. In this case it is receptors rather than neurons which are activated: if the photostimulation was applied directly to the afferent axons, the modulation of firing rate was small or absent in contrast to the sensitive response from stimulating receptors. However this group has recently reported that in the cochlea, afferent neurons in the spiral ganglion are activated by similar low level pulsed IR and that cochlear result is now being explored as a new means of stimulation by an optical cochlear implant (Rajguru et al. 2010). This innovative work has taken place in toadfish semicircular canal receptors because the toadfish inner ear is relatively more accessible than those of mammals and because, thanks to the work of this group, so much is now known about the physiology of the semicircular canal receptors in this species. However, in the toadfish the vestibular hair cell receptor types differ from those in mammals and their vestibular efferents function rather differently from those in mammals, so one looks forward to the extension of these results to mammalian vestibular systems. How does this modulation occur? Of course the reader's first thought will be that this is an artifact due to high intensity laser stimulation causing a mechanical or a thermal change and so activating the hair cell. In fact it is a very low power laser and the authors report a series of elegant experiments to show thermal and opto-mechanical factors are not the cause of the response. Afferents activated by photostimulation did not respond to thermal stimuli which caused approximately equivalent temperature increases of the sensory epithelium. It is not some opto-mechanical artifact, since the latency of the afferent response (about 7.6 ms to a 200 μs pulse) is unaffected by intensity. The long latency is much too long to be a synaptic delay, which is about 0.6 ms at the toadfish hair cell-afferent synapse (Rabbitt et al. 1995). The long delay excludes the possibility that the stimulation is due to direct depolarization of the hair cells by light and it supports their hypothesis of a photo-activated signalling mechanism internal to the hair cell. The authors conclude that the IR pulse is changing the excitability of the receptor hair cells, most probably by changing Ca2+ signalling within the receptor cells. All receptor hair cells on the crista have exactly the same morphological polarization, so one would expect uniform responses to photostimulation, but that was not found; some afferents were excited, some were inhibited. Their experiments exclude a number of possible reasons for these opposite effects, including a direct role for the vestibular efferents. The authors suggest that the inhibitory effects may be due to changes in K+ channels hyperpolarizing some hair cells. Photostimulation of vestibular receptors has great potential for future clinical application. Using light to activate receptors and neurons has great advantages. The optical fibre is electrically isolated and not subject to the same tissue/electrode interface problems associated with electrical stimulation via metal electrodes as is used for cochlear implants. Using light may result in a vestibular prosthesis which is not subject to the ageing problem of metal cochlear implants – as the implant ages, increasing current is needed to generate equivalent neural activation, causing faster degradation of the electrode. In the field of sensory physiology, the cochlear implant is the benchmark for translation of basic physiological knowledge to clinical application. The vestibular receptors are in the same labyrinth, just a few millimetres away from the cochlear receptors and their afferents travel with the cochlear afferents in the eighth nerve. But the contrast between the cochlear and vestibular prosthetic application is profound – it is estimated that over 100,000 patients have benefitted from receiving cochlear implants, but it was only on 21 October 2010 that Jay Rubinstein of the University of Washington, Seattle, implanted the very first (electrical) vestibular implant into the labyrinth of a patient to alleviate incapacitating vertigo attacks due to Ménière's disease. There is no doubt that many other vestibular implants will follow. Activation of vestibular receptors by light may be a means by which they work.