Non-technical summary We have investigated the mechanisms underlying the response of cells to pulsed infrared radiation (IR, ∼1862 nm) using the neonatal rat ventricular cardiomyocyte as a model. n = 12), an inhibitor of the mitochondrial Na + /Ca 2+ exchanger (mNCX), (2) Ruthenium Red (40 μM, n = 13), an inhibitor of the mitochondrial Ca 2+ uniporter (mCU), and (3) 2-aminoethoxydiphenylborane (10 μM, n = 6), an IP 3 channel antagonist. Ryanodine blocked the spontaneous [Ca 2+ ] i transients but did not alter the IR-evoked events in the same cells. This pharmacological array implicates mitochondria as the major intracellular store of Ca 2+ involved in IR-evoked responses reported here. Results support the hypothesis that 1862 nm pulsed IR modulates mitochondrial Ca 2+ transport primarily through actions on mCU and mNCX.
Infrared neural stimulation (INS) has received considerable attention over the last few years. It provides an alternative method to artificially stimulate neurons without electrical current or the introduction of exogenous chromophores. One of the primary benefits of INS could be the improved spatial selectivity when compared with electrical stimulation. In the present study, we have evaluated the spatial selectivity of INS in the acutely damaged cochlea of guinea pigs and compared it to stimulation with acoustic tone pips in normal hearing animals. The radiation was delivered via a 200 μm-diameter optical fiber, which was inserted through a cochleostomy into the scala tympani of the basal cochlear turn. The stimulated section along the cochlear spiral ganglion was estimated from the neural responses recorded from the central nucleus of the inferior colliculus (ICC). ICC responses were recorded in response to cochlear INS using a multichannel penetrating electrode array. Spatial tuning curves were constructed from the responses. For INS, approximately 55% of the activation profiles showed a single maximum, ~22% had two maxima, and ~13% had multiple maxima. The remaining 10% of the profiles occurred at the limits of the electrode array and could not be classified. The majority of ICC spatial tuning curves indicated that the spread of activation evoked by optical stimuli is comparable to that produced by acoustic pips.
Non-technical summary It has been shown previously that application of short pulses of optical energy at infrared wavelengths can evoke action potentials in neurons and mechanical contraction in cardiac muscle cells. Optical stimuli are particularly attractive because of the ability to deliver focused energy through tissue without physical contact or electrical charge injection. Here we demonstrate efficacy of pulsed infrared radiation to stimulate balance organs of the inner ear, specifically to modulate the pattern of neural signals transmitted from the angular motion sensing semicircular canals to the brain. The ability to control action potentials demonstrates the potential of pulsed optical stimuli for basic science investigations and future therapeutic applications. AbstractThe present results show that the semicircular canal crista ampullaris of the toadfish, Opsanus tau, is sensitive to infrared radiation (IR) applied in vivo. IR pulse trains (∼1862 nm, ∼200 μs pulse −1 ) delivered to the sensory epithelium by an optical fibre evoked profound changes in phasic and tonic discharge rates of postsynaptic afferent neurons. Phasic afferent responses to pulsed IR occurred with a latency of <8 ms while tonic responses developed with a time constant (τ) of 7 ms to 10 s following the onset or cessation of the radiation. Afferents responded to direct optical radiation of the sensory epithelium but did not respond to thermal stimuli that generated nearly equivalent temperature increases of the whole organ. A subset of afferent neurons fired an action potential in response to each IR pulse delivered to the sensory epithelium, at phase-locked rates up to 96 pulses per second. The latency between IR pulses and afferent nerve action potentials was much greater than synaptic delay and spike generation, demonstrating the presence of a signalling delay interposed between the IR pulse and the action potential. The same IR stimulus applied to afferent nerve axons failed to evoke responses of similar magnitude and failed to phase-lock afferent nerve action potentials. The present data support the hypothesis that pulsed IR activates sensory hair cells, thus leading to modulation of synaptic transmission and afferent nerve discharge reported here.
The cochlear implant (CI) is the first effective treatment for deafness and severe losses in hearing. As such, the CI is now widely regarded as one of the great advances in modern medicine. This paper reviews the key events and discoveries that led up to the current CI systems, and we review and present some among the many possibilities for further improvements in device design and performance. The past achievements include: (1) development of reliable devices that can be used over the lifetime of a patient; (2) development of arrays of implanted electrodes that can stimulate more than one site in the cochlea; and (3) progressive and large improvements in sound processing strategies for CIs. In addition, cooperation between research organizations and companies greatly accelerated the widespread availability and use of safe and effective devices. Possibilities for the future include: (1) use of otoprotective drugs; (2) further improvements in electrode designs and placements; (3) further improvements in sound processing strategies; (4) use of stem cells to replace lost sensory hair cells and neural structures in the cochlea; (5) gene therapy; (6) further reductions in the trauma caused by insertions of electrodes and other manipulations during implant surgeries; and (7) optical rather electrical stimulation of the auditory nerve. Each of these possibilities is the subject of active research. Although great progress has been made to date in the development of the CI, including the first substantial restoration of a human sense, much more progress seems likely and certainly would not be a surprise.
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