Abstract
Recent studies have shown that ionic direct current (iDC) can modulate the vestibular system in-vivo, with potential benefits over conventional pulsed stimulation. In this study, the effects of iDC stimulation on vestibular nerve fiber firing rate was investigated using loose-patch nerve fiber recordings in the acutely excised mouse crista ampullaris of the semicircular canals. Cathodic and anodic iDC steps instantaneously reduced and increased afferent spike rate, with the polarity of this effect dependent on the position of the stimulating electrode. A sustained constant anodic or cathodic current resulted in an adaptation to the stimulus and a return to spontaneous spike rate. Post-adaptation spike rate responses to iDC steps were similar to pre-adaptation controls. At high intensities spike rate response sensitivities were modified by the presence of an adaptation step. Benefits previously observed in behavioral responses to iDC steps delivered after sustained current may be due to post-adaptation changes in afferent sensitivity. These results contribute to an understanding of peripheral spike rate relationships for iDC vestibular stimulation and validate an ex-vivo model for future investigation of cellular mechanisms. In conjunction with previous in-vivo studies, these data help to characterize iDC stimulation as a potential therapy to restore vestibular function after bilateral vestibulopathy.
Highlights
Recent studies have shown that ionic direct current can modulate the vestibular system invivo, with potential benefits over conventional pulsed stimulation
An invasive stimulation approach is necessary in order to activate specific vestibular canals. An evolution of this concept is the focused, safe delivery of ionic direct current separately into each vestibular semicircular canal through an electrolyte-filled microcatheter with the intent to restore functional vestibular sensation for patients suffering from bilateral vestibular dysfunction9–11. iDC has an advantage over traditional pulse-based neuro-stimulation, in that iDC can excite or inhibit the vestibular system depending on the polarity of the stimulating current[12]
It has been well established from the field of trans-cranial DC stimulation that the relative distribution and magnitude of an artificially generated electric field dramatically influences the relationship between stimulus and neural response[14,15,16,17]
Summary
Recent studies have shown that ionic direct current (iDC) can modulate the vestibular system invivo, with potential benefits over conventional pulsed stimulation. Benefits previously observed in behavioral responses to iDC steps delivered after sustained current may be due to post-adaptation changes in afferent sensitivity These results contribute to an understanding of peripheral spike rate relationships for iDC vestibular stimulation and validate an ex-vivo model for future investigation of cellular mechanisms. IDC stimulation was performed in the acutely excised mouse crista ampullaris, while monitoring afferent firing rates with extracellular loose-patch recordings from vestibular nerve fiber endings In this experimental setting, the effects of stimulator position and short and long duration iDC step modulation on afferent activity were examined. These data provide important insights for future design of iDC stimulation paradigms and validate the ex-vivo preparation as a model system that will allow further investigation of underlying intracellular mechanisms of DC vestibular stimulation
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