Intact Semicircular Canal Research Articles

Sensory transduction at the frog semicircular canal: how hair cell membrane potential controls junctional transmission.

At the frog semicircular canals, the afferent fibers display high spontaneous activity (mEPSPs), due to transmitter release from hair cells. mEPSP and spike frequencies are modulated by stimulation that activates the hair cell receptor conductance. The relation between receptor current and transmitter release cannot be studied at the intact semicircular canal. To circumvent the problem, we combined patch-clamp recordings at the isolated hair cell and electrophysiological recordings at the cytoneural junction in the intact preparation. At isolated hair cells, the K channel blocker tetraethylammonium (TEA) is shown to block a fraction of total voltage-dependent K-conductance (IKD) that depends on TEA concentration but not on membrane potential (Vm). Considering the bioelectric properties of the hair cell, as previously characterized by this lab, a fixed fractional block of IKD is shown to induce a relatively fixed shift in Vm, provided it lies in the range −30 to −10 mV. The same concentrations of TEA were applied to the intact labyrinth while recording from single afferent fibers of the posterior canal, at rest and during mechanical stimulation. At the peak of stimulation, TEA produced increases in mEPSP rate that were linearly related to the shifts produced by the same TEA concentrations (0.1–3 mM) in hair cell Vm (0.7–5 mV), with a slope of 29.8 Hz/mV. The membrane potential of the hair cell is not linearly related to receptor conductance, so that the slope of quantal release vs. receptor conductance depends on the prevailing Vm (19.8 Hz/nS at −20 mV; 11 Hz/nS at −10 mV). Changes in mEPSP peak size were negligible at rest as well as during stimulation. Since ample spatial summation of mEPSPs occurs at the afferent terminal and threshold-governed spike firing is intrinsically nonlinear, the observed increases in mEPSP frequency, though not very large, may suffice to trigger afferent spike discharge.

Semicircular canal-dependent developmental tuning of translational vestibulo-ocular reflexes in Xenopus laevis.

Gaze stabilization during head/body movements is achieved to a large extent by vestibular-evoked compensatory eye movements. These reflexes derive from semicircular canal and otolith organs and depend on the transformation of the respective sensory signals into extraocular motor commands. To elicit directionally and dynamically appropriate compensatory eye movements, extraocular motoneurons require spatiotemporally specific inputs from semicircular canals and regions of the utricular epithelium with matching directional sensitivity. The ontogenetic establishment and maturation of the directional tuning of otolith inputs in extraocular motoneurons was studied in Xenopus laevis tadpoles. In young larvae at stage 46-48, superior oblique (SO) extraocular motoneurons receive omnidirectional utricular signals during horizontal translational motion, indicating an absence of spatial tuning. In contrast, in older larvae beyond stage 49 these motoneurons were activated by directionally more restricted otolith inputs with an increasingly enhanced spatial tuning until stage 53. This developmental process limited the origin of otolith signals to a utricular epithelial sector with a hair cell sensitivity that is coaligned with the pulling direction of the SO eye muscle. The maturation of the otolith response vector was abolished by enzymatic prevention of semicircular canal formation in postembryonic tadpoles at stage 44, suggesting that functionally intact semicircular canals are causally responsible for the observed directional tuning of utricular responses. A likely mechanism by which semicircular canals might influence the tuning of the otolith responses includes stabilization of coactivated and centrally converging sensory signals from semicircular canal and spatially aligned epithelial utricular regions during natural head/body motion.

Neurotological and Neuroanatomical Changes in the Connexin-26-Related HID/KID Syndrome

The phenotype of the HID (hystrix-like ichthyosis, deafness)/KID (keratitis, ichthyosis, deafness) syndrome is primarily characterized by skin changes. However, the connexin 26 (Cx 26) autosomal dominant mutation underlying this syndrome is of special neurotological interest. In the present paper, the clinical pattern, audiovestibular and neuroimaging findings and the detailed genetic analysis of 4 patients with identical HID/KID-associated mutation D50N of Cx 26 are reported. The audiological test results demonstrated profound sensorineural hearing loss in all of the patients. Neurotological testing revealed inconsistent abnormalities in dynamic posturography (sensory organization test), but the vestibular ocular reflex upon caloric irrigation was normal in all patients. Vestibular-evoked myogenic potential testing for otolith function (saccule) showed a regular response in 1 patient and pathologic responses in 3 patients, while subjective haptic vertical (utricular function) testing was normal in all of the patients. CCT showed an extended (in length), but very thin (in diameter) bony lining between the basal portion of the internal auditory canal and the vestibule in the 3 scanned patients. Our study provides evidence for functionally intact semicircular canals and normal utricular function in subjects with the autosomal dominant D50N mutation of Cx 26, in contrast to saccular function which was generally compromised and hearing loss which was profound.

The effects of unilateral eighth nerve block on fictive VOR in the turtle

Multiunit activity during horizontal sinusoidal motion was recorded from pairs of oculomotor, trochlear, or abducens nerves of an in vitro turtle brainstem preparation that received inputs from intact semicircular canals. Responses of left oculomotor, right trochlear and right abducens nerves were approximately aligned with leftward head velocity, and that of the respective contralateral nerves were in-phase with rightward velocity. We examined the effect of sectioning or injecting lidocaine (1–2 μL of 0.5%) into the right vestibular nerve. Nerve block caused a striking phase shift in the evoked response of right oculomotor and left trochlear nerves, in which (rightward) control responses were replaced by a smaller-amplitude response to leftward table motion. Such “phase-reversed” responses were poorly defined in abducens nerve recordings. Frequency analysis demonstrated that this activity was advanced in phase relative to post-block responses of the respective contralateral nerves, which were in turn phase-advanced relative to pre-block controls. Phase differences were largest (∼10°) at low frequencies (∼0.1 Hz) and statistically absent at 1 Hz. The phase-reversed responses were further investigated by eliminating individual canal input from the left labyrinth following right nVIII block, which indicated that the activation of the vertical canal afferents is the source of this activity.

Surgical management of special cases of intractable Meniere's disease: unilateral cases with intact canals and bilateral cases.

If a clinician seeks to allow patients with vertigo to return to work as soon as possible, it is very important to determine the appearance of vestibular symptoms during convalescence just after treatment, as well as the long-term results. Apprehensive patients with vertigo may undergo severe psychological torment if treatment requires long-term rest in bed before they can return to daily life. In this paper, we observed postoperative vestibular symptoms (subjective sensation and objective nystagmus) in 50 patients with intractable Meniere's disease, including cases from our previous preliminary report, during the period of convalescence just after endolymphatic sac drainage and steroid instillation surgery (EDSS). All symptoms were eliminated within 8 days after EDSS. There was no significant difference in the duration of any vestibular symptoms between bilateral (n = 8) and unilateral cases (n = 42). This result indicates that EDSS could be as safe a treatment for bilateral Meniere's disease as for unilateral disease. In unilateral cases with intact semicircular canal function (n = 17), postoperative evoked vestibular sensation, positional, and positioning (Dix-Hallpike) nystagmus disappeared significantly earlier than in those with canal paresis (n = 25). This result indicates that EDSS could keep the vestibular peripheral function of patients with unilateral Meniere's disease with intact canals quite stable after surgery. Therefore, EDSS could be recommended as an initial, less-invasive surgical treatment for intractable Meniere's disease, especially in unilateral cases with intact canals and in bilateral cases.

Impulsive testing of individual semicircular canal function.

In order to test the human angular vestibulo-ocular reflex in the dynamic range of normal head movements, we measured 3-dimensional compensatory eye-movement responses to low-amplitude (10-12 degrees), high-acceleration (3000-4000 degrees/s/s), passive, manually delivered head rotations (head "impulses") in the three planes of the semicircular canals in normal subjects, in subjects who had recovered from surgical unilateral vestibular deafferentation, and in patients after acute unilateral peripheral vestibulopathy, that is, from vestibular "neuritis." We found that canal-plane head impulses away from an intact semicircular canal, that is, toward a lesioned semicircular canal, invariably produce a vestibulo-ocular reflex with permanently low gain, typically less that 0.4 if the lesion is complete. These results are a necessary consequence of primary semicircular canal afferents being driven into inhibitory saturation by rapid angular accelerations. With practice, clinicians can learn to recognize the telltale compensatory saccades that patients with unilateral loss of semicircular canal function will make if asked to look at an earth-fixed target during head impulses in any one of the three semicircular canal planes.

Differential processing of semicircular canal signals in the vestibulo- ocular reflex

Selective semicircular canal inactivation and three-dimensional eye movement recordings have been used to investigate the spatial organization of vestibular signals in the vestibulo-ocular reflex (VOR) of rhesus monkeys. In animals with one pair of semicircular canals inactivated, afferent activity no longer codes all spatial components of head angular velocity. if it were the activation pattern of semicircular canal afferents alone that determines VOR slow phase eye velocity, the head velocity components along the sensitivity vectors of the remaining intact semicircular canals would determine the orientation of slow phase eye velocity. Thus, angular head velocity and slow phase eye velocity would not necessarily always align. Alternatively, if vestibulo-ocular signals coded absolute angular head motion in space based on both semicircular canal and otolith afferent information, one might expect a spatial transformation of the encoded head angular velocity signals such that slow phase eye velocity and angular head velocity continue to spatially align. Examination of the VOR at different frequencies between 0.01 Hz and 1 Hz revealed a frequency-specific spatial organization of vestibulo-ocular signals. Mid and high frequency vestibulo-ocular responses were determined exclusively by the orientation of the sensitivity vectors of the remaining intact semicircular canals. In contrasts, low frequency vestibulo-ocular responses were largely determined by the orientation of the head relative to gravity. These low frequency responses after selective semicircular canal inactivation could be predicted and simulated by a simple model where semicircular canal signals are spatially transformed from a head-fixed to a space-fixed (inertial) representation of angular head velocity. These findings suggest that low frequency vestibulo-ocular responses are dominated by inertial vestibular signals that detect absolute head motion in space based on both semicircular canal and otolith afferent information. Inertial vestibular signals are likely to contribute to head control and motor coordination of gaze, head and body posture.

Recording of short-latency vestibular evoked potentials induced by acceleration impulses in experimental animals: current status of the method and its applications

The short-latency vestibular evoked potential (VsEP) induced by angular acceleration impulses (maximal amplitude 30,000 deg/sec 2, rise time 2–3 msec) was recorded by skin electrodes in intact cats after various surgical and pharmacological procedures. The normal VsEP consists of 5–8 waves, several microvolts in amplitude, during the first 10 msec. The latency of the first wave (P1) is about 2 msec with respect to the start of head acceleration. The first and the second waves (P1 and P2) were shown to originate from the vestibular nerve and nucleus, respectively. The VsEP disappears permanently after bilateral labyrinthectomy, excision of the 8th nerves, or administration of large doses of gentamicin. Temporary disappearance is caused by anoxia induced for a brief period of time or injection of lidocaine (4%) into the vestibular nerve or into the inner ear after contralateral labyrinthectomy. The VsEPs in the intact cat are similar whether clockwise or counterclockwise stimuli are used and are not affected by changing the position of the head. Unilaterally labyrinthectomized animals, however, show asymmetric response whereby excitatory stimulation of any of the intact semicircular canals evokes prominent P1 and P2 waves which are absent with inhibitory stimulation. The rate and input-output intensity functions of the VsEP are described. The threshold of the VsEP was found to be 1000–1500 deg/sec 2. In addition to the neurogenic waves, 2 other potentials appear occasionally in the response: (1) large-amplitude and longer-duration waves with latencies of 8–20 msec, which are of myogenic origin, and (2) smaller waves with shorter latency which probably represent vestibular microphonics and generator potentials. Extracellular recordings of the responses of single second-order neurons in the vestibular nuclei to the same acceleration impulses confirmed that the kinetic vestibular neurons can respond to these stimuli with a latency as short as 3.5 msec. This method for inducing and recording VsEPs has proved to be a powerful tool for the evaluation of vestibular function in experimental animal models.