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Vestibular afferent neurons convey information from hair cells in the peripheral vestibular end organs to central nuclei. Primary vestibular afferent neurons can fire action potentials at high rates and afferent firing patterns vary with the position of nerve terminal endings in vestibular neuroepithelia. Terminals contact hair cells as small bouton or large calyx endings. To investigate the role of Na + currents ( I Na ) in firing mechanisms, we investigated biophysical properties of I Na in calyx-bearing afferents. Whole cell patch-clamp recordings were made from calyx terminals in thin slices of gerbil crista at different postnatal ages: immature [postnatal day (P)5-P8, young (P13-P15), and mature (P30-P45)]. A large transient Na + current ( I NaT ) was completely blocked by 300 nM tetrodotoxin (TTX) in mature calyces. In addition, I NaT was accompanied by much smaller persistent Na + currents ( I NaP ) and distinctive resurgent Na + currents ( I NaR ), which were also blocked by TTX. ATX-II, a toxin that slows Na + channel inactivation, enhanced I NaP in immature and mature calyces. 4,9-Anhydro-TTX (4,9-ah-TTX), which selectively blocks Nav1.6 channels, abolished the enhanced I Na in mature, but not immature, calyces. Therefore, Nav1.6 channels mediate a component of I NaT and I NaP in mature calyces, but are minimally expressed at early postnatal days. I NaR was expressed in less than one-third of calyces at P6-P8, but expression increased with development, and in mature cristae I NaR was frequently found in peripheral calyces. I NaR served to increase the availability of Na + channels following brief membrane depolarizations. In current clamp, the rate and regularity of action potential firing decreased in mature peripheral calyces following 4,9-ah-TTX application. Therefore, Nav1.6 channels are upregulated during development, contribute to I NaT , I NaP, and I NaR , and may regulate excitability by enabling higher mean discharge rates in a subpopulation of mature calyx afferents. NEW & NOTEWORTHY Action potential firing patterns differ between groups of afferent neurons innervating vestibular epithelia. We investigated the biophysical properties of Na + currents in specialized vestibular calyx afferent terminals during postnatal development. Mature calyces express Na + currents with transient, persistent, and resurgent components. Nav1.6 channels contribute to resurgent Na + currents and may enhance firing in peripheral calyx afferents. Understanding Na + channels that contribute to vestibular nerve responses has implications for developing new treatments for vestibular dysfunction.

Infrared laser irradiation has been established as an appropriate stimulus for primary sensory neurons under conditions where sensory receptor cells are impaired or lost. Yet, development of clinical applications has been impeded by lack of information about the molecular mechanisms underlying the laser-induced neural response. Here, we directly address this question through pharmacological characterization of the biological response evoked by midinfrared irradiation of isolated retinal and vestibular ganglion cells from rodents. Whole cell patch-clamp recordings reveal that both voltage-gated calcium and sodium channels contribute to the laser-evoked neuronal voltage variations (LEVV). In addition, selective blockade of the LEVV by micromolar concentrations of ruthenium red and RN 1734 identifies thermosensitive transient receptor potential vanilloid channels as the primary effectors of the chain reaction triggered by midinfrared laser irradiation. These results have the potential to facilitate greatly the design of future prosthetic devices aimed at restoring neurosensory capacities in disabled patients.

Melatonin has been reported to decrease nerve activity of medial vestibular nuclei in the rat and is associated with attenuated muscle sympathetic nerve activity (MSNA) responses to baroreceptor unloading in humans. The purpose of this study was to determine if melatonin alters the vestibulosympathetic reflex (VSR) and vestibulocollic reflex (VCR) in humans. In study 1, MSNA, arterial blood pressure, and heart rate were measured in 12 healthy subjects (28 ± 1 yr; 6 men, 6 women) during head-down rotation (HDR) before and 45 min after ingestion of either melatonin (3 mg) or placebo (sucrose). Subjects returned at least 2 days later at the same time of day to repeat the trial after ingesting the opposite treatment (melatonin or placebo). Melatonin significantly attenuated MSNA responses during HDR compared with placebo (burst frequency Δ 4 ± 1 vs. Δ 7 ± 1 bursts/min, and total MSNA Δ 51 ± 20 and Δ 96 ± 15%, respectively; P < 0.02). In study 2, vestibular evoked myogenic potentials (VEMP) were measured in 10 healthy subjects (26 ± 1 yr; 4 men and 6 women) before and after ingestion of 3 mg melatonin. Melatonin did not alter the timing of the p13 and n23 peaks (pre-melatonin 13.2 ± 0.4 and 21.3 ± 0.6 ms vs. post-melatonin 13.5 ± 0.4 and 21.4 ± 0.7 ms, respectively) or the p13-n23 interpeak amplitudes [pre-melatonin 22.5 ± 4.6 arbitrary units (au) and post-melatonin 22.7 ± 4.6 au]. In summary, melatonin attenuates the VSR and supports the concept that melatonin negatively affects orthostatic tolerance. However, melatonin does not alter the VCR in humans suggesting melatonin's effect on the VSR appears to be mediated by the utricles.

Avian auditory and vestibular hair cells regenerate after damage by ototoxic drugs, but until recently there was little evidence that regenerated vestibular hair cells function normally. In an earlier study we showed that the vestibuloocular reflex (VOR) is eliminated with aminoglycoside antibiotic treatment and recovers as hair cells regenerate. The VOR, which stabilizes the eye in the head, is an open-loop system that is thought to depend largely on regularly firing afferents. Recovery of the VOR is highly correlated with the regeneration of type I hair cells. In contrast, the vestibulocolic reflex (VCR), which stabilizes the head in space, is a closed-loop, negative-feedback system that seems to depend more on irregularly firing afferent input and is thought to be subserved by different circuitry than the VOR. We examined whether this different reflex also of vestibular origin would show similar recovery after hair cell regeneration. Lesions of the vestibular hair cells of 10-day-old chicks were created by a 5-day course of streptomycin sulfate. One day after completion of streptomycin treatment there was no measurable VCR gain, and total hair cell density was approximately 35% of that in untreated, age-matched controls. At 2 wk postlesion there was significant recovery of the VCR; at this time two subjects showed VCR gains within the range of control chicks. At 3 wk postlesion all subjects showed VCR gains and phase shifts within the normal range. These data show that the VCR recovers before the VOR. Unlike VOR gain, recovering VCR gain correlates equally well with the density of regenerating type I and type II vestibular hair cells, except at high frequencies. Several factors other than hair cell regeneration, such as length of stereocilia, reafferentation of hair cells, and compensation involving central neural pathways, may be involved in behavioral recovery. Our data suggest that one or more of these factors differentially affect the recovery of these two vestibular reflexes.

Spontaneous activity from 120 vestibular semicircular canal (SC) primary afferents and driven responses from 20 SC primary afferents to 2.3-decade bandwidth (0.029-6.152 Hz) sum of sinusoidal angular rotations were characterized in 10 unanesthetized pigeons. The results were compared with those previously gathered from barbiturate anesthetized pigeons. The average spontaneous mean firing rate (MFR) of SC primary afferents in unanesthetized pigeons was found to be 168 impulses per second (I/s), n = 120, and is approximately 80% higher than that for SC primary afferents in anesthetized pigeons [93 I/s, n = 149 (Ref. 9) and 92 I/s, n = 124 (Ref. 22)]. The spontaneous discharge of SC primary afferents from unanesthetized pigeons was classified according to the coefficient of variation (CV) of 512-1,024 interspike intervals (ISIs) into regular (CV less than 0.1), intermediate (0.1 less than or equal to CV less 0.4), and irregular (0.4 less than or equal to CV) categories. The percentages of SC primary afferents falling within each CV category were similar for unanesthetized and anesthetized pigeons (22). The relation between the spontaneous mean ISI and its standard deviation (SD) for SC primary afferents in the unanesthetized pigeon is best described by a power function model, which provides a significantly better fit than does a linear model. The parameters of this power function model are similar for SC primary afferents in unanesthetized and anesthetized pigeons (10). The spontaneous ISIs of individual SC primary afferents in the unanesthetized pigeon were found to be distributed either normally, log-normally, or according to the first passage time of the Wiener-Levy (WL) process. The gain of anterior SC primary afferents at 0.25 Hz is similar for anesthetized (2.93 I X s-1 X deg-1 X s-1, n = 14) (11) and for unanesthetized (3.01 I X s-1 X deg-1 X s-1, n = 14) pigeons. Bode plots constructed from the responses to sum sinusoidal angular accelerations reveal that SC primary afferents in unanesthetized pigeons display a phase lead and gain enhancement at frequencies between 0.6 and 6 Hz.(ABSTRACT TRUNCATED AT 400 WORDS)