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Background: This paper discusses some of the concepts and major physiological issues in developing a means of electrically stimulating the otolithic system, with the final goal being the electrical stimulation of the otoliths in human patients. It contrasts the challenges of electrical stimulation of the otolith organs as compared to stimulation of the semicircular canals. Electrical stimulation may consist of trains of short-duration pulses (e.g., 0.1 ms duration at 400 Hz) by selective electrodes on otolith maculae or otolithic afferents, or unselective maintained DC stimulation by large surface electrodes on the mastoids – surface galvanic stimulation. Summary: Recent anatomical and physiological results are summarized in order to introduce some of the unique issues in electrical stimulation of the otoliths. The first challenge is that each otolithic macula contains receptors with opposite polarization (opposing preferred directions of stimulation), unlike the uniform polarization of receptors in each semicircular canal crista. The puzzle is that in response to the one linear acceleration in the one macula, some otolithic afferents have an increased activation whereas others have decreased activation. Key Messages: At the vestibular nucleus this opposite receptor hair cell polarization and consequent opposite afferent input allow enhanced response to the one linear acceleration, via a “push-pull” neural mechanism in a manner analogous to the enhancement of semicircular canal responses to angular acceleration. Within each otolithic macula there is not just one uniform otolithic neural input to the brain – there are very distinctly different channels of otolithic neural inputs transferring the neural data to the brainstem. As a simplification these channels are characterized as the sustained and transient systems. Afferents in each system have different responses to stimulus onset and maintained stimulation and likely different projections, and most importantly different thresholds for activation by electrical stimulation and different adaptation rates to maintained stimulation. The implications of these differences are considered.

Objective: The aim of this work was to describe the dimensions of the crista fenestra and determine its presence by means of high-resolution computed tomography (CT) for the purpose of cochlear implantation via the round window approach. Methods: A series of 10 adult human temporal bones underwent high-resolution CT scanning and were further dissected for microscopic study of the round window niche. Results: In all of the specimens, the round window membrane was fully visualized after the complete removal of bony overhangs. The crista fenestra was identified as a sharp bony crest located in the anterior and inferior borders of the niche; its area ranged from 0.28 to 0.80 mm2 (mean 0.51 ± 0.18). The proportion of the area occupied by the crista fenestra in the whole circumference of the round window ranged from 23 to 50% (mean 36%). We found a moderate positive correlation between the area of the niche and the dimensions of the crista fenestra (Spearman rho: 0.491). In every case, high-resolution CT scanning was unable to determine the presence of the crista fenestra. Conclusion: The crista fenestra occupies a variable but expressive area within the bony round window niche. Narrower round window niches tended to house smaller crests. The presence of the crista fenestra is an important obstacle to adequate access to the scala tympani. Nevertheless, a high-resolution CT scan provides no additional preoperative information with regard to its presence for the purpose of surgical access to the scala tympani via the round window niche.

Significant ototoxicity limits the use of aminoglycoside (AG) antibiotics. Several mechanisms may contribute to the death of both auditory and vestibular hair cells. In this study the effects of gentamicin and neomycin on K+ currents in mature and early postnatal type I vestibular hair cells (HCI) were tested directly. The whole-cell patch clamp technique was used to assess the effects of AG and KCNQ channel modulators on K+ currents (IK) in HCI acutely isolated from gerbil semicircular canals. Extracellular neomycin (1 mM) rapidly reduced peak outward IK by 16 ± 4% (n = 9) in mature HCI (postnatal days, P, 25-66). Gentamicin (5 mM) reduced outward IK by 16 ± 3% (n = 8). A similar reduction in outward current was seen in immature HCI (P5-9) that lacked the low-voltage-activated component of IK observed in mature cells. Intracellular application of gentamicin and neomycin also reduced IK in mature HCI. Modulators of KCNQ channels were used to probe KCNQ channel involvement. The selective KCNQ antagonist XE991 did not reduce IK and the neomycin-induced reduction in IK was not reversed by the KCNQ agonist flupirtine. Application of intracellular poly-D-lysine to sequester PIP2 did not reduce IK. Application of the K+ channel blocker 4-aminopyridine (4-AP) strongly reduced IK, and extracellular AG in the presence of 4-AP gave no further inhibition of IK. In summary, AG significantly reduce the 4-AP-sensitive IK in early postnatal and mature HCI. K+ current inhibition differs from that seen in outer hair cells, since it does not appear to involve PIP2 sequestration or KCNQ channels.

Objective: Our aim was to investigate the relationship between the distribution of the dermoscopic patterns seen in plantar melanocytic nevi and the 3-dimensional structures of the epidermis. Methods: The precise locations of 69 melanocytic nevi on the sole and the border areas were investigated, with attention paid to each dermoscopic pattern. In addition, the basal surfaces of the plantar epidermis from 14 anatomical areas were observed by scanning electron microscopy (SEM). Results: In the weight-bearing area, melanocytic nevi with a fibrillar pattern were preferentially observed. Those with a lattice-like pattern were observed in the arch area, whereas those with a crista reticulated pattern were seen in the border area. On SEM observations, transverse ridges formed a couple of parallel lamellae on the crista profunda limitans (limiting ridges). Between the limiting ridges and the crista profunda intermedia (intermediate ridges), the transverse ridges had different shapes according to the anatomical location of the sole. Conclusion: These results suggest that the characteristic dermoscopic patterns seen in plantar melanocytic nevi simulate the arrangement of transverse ridges.

Spontaneous discharge patterns of first-order canal afferents were analyzed in cats anethetized with pentobarbital sodium with particular emphasis on the relationship of regularity of resting discharge, sensitivity to angular acceleration and adaptation to the time delay between electrical labyrinthine stimulation and recording from afferents near Scarpa's ganglion. Regular units were found to have a high resting rate, low sensitivity to angular acceleration, were mostly nonadapting during prolonged acceleration and showed relatively long latency to electrical stimulation. Irregular units tended to have a low resting rate, high sensitivity, frequently showed adaptation and had short latencies. Intermediate neurons had mixed characteristics of regular and irregular units. In medulated nerve fibers, a direct relation exists between conduction velocity and fiber diameter. As latency is due primarily to conduction in the first-order axon, we may speculate that regular neurons have thin fibers which innervate the slope of the crista, irregular neurons have thick fibers which innervate the summit, and intermediate units have medium caliber fibers which innervate both the slope and summit of the crista ampullaris.

The topographic arrangement of vestibular nerve fibers innervating semicircular canal cristae of the chinchilla was studied using computer-aided video-microscopy and three-dimensional reconstruction. At the level 20 microns proximal to the base of the crista, bundles consisting of 30-50 nerve fibers each were identified. Nerve fibers in bundles were classified into seven categories depending on the diameter. We confirmed that large nerve fibers were more frequently found in the central bundles and small nerve fibers were more frequently found in the peripheral bundles. The central bundle might function as a physiological unit coding various types of head movements, whereas the peripheral bundle might contribute more to the detection of slow and long-lasting movements giving rise to tonus and posture changes. The canalicular nerve may code rotational acceleration of the head via function- and locus-specific nerve fiber bundles.

Carboplatin, a second-generation platinum drug used in the treatment of cancer, can damage the hair cells in the vestibular system; however, little is known about the time course of its vestibulotoxic effects. The present study examined the acute vestibulotoxic effects of carboplatin (50 mg/kg) in the chinchilla. The duration of the nystagmus response evoked by cold caloric stimulation was significantly reduced 6 h following carboplatin treatment and showed a maximum, permanent reduction of approximately 50% by 24 h after injection. Light-microscopic observations at 6 h subsequent to injection revealed swollen afferent dendrites beneath type-I hair cells and the appearance of small vacuoles within the type-I hair cells; these changes were most pronounced in the crista ampullaris of the semicircular canals compared to the maculae of the utricle and saccule. Many mitochondria were swollen and partially depleted of their membranous infoldings. The mitochondrial abnormalities tended to be somewhat more severe in the hair cells than in their afferent terminals. The structural abnormalities in the mitochondria were more severe at 24 h following injection resulting in the appearance of larger and more numerous vacuoles in the hair cells. By 3 days after injection, many type-I hair cells were filled with large vacuoles which often caused severe distortion of the nucleus and disruption of the plasma membrane. Small vacuoles were occasionally observed in type-II hair cells, mainly in the crista ampullaris. These results indicate that the vestibulotoxic effects of carboplatin occur quite rapidly and cause significant disruption of the mitochondria in hair cells and their afferent terminals.

A comparative morphometric study of ventricular myocardial cells of the West African insect-eating bat, Pipistrellus pipistrellus the hamster and the rat revealed significant differences in volume fractions of mitochondria, myofibrils, lipid bodies and T tubules. In the cells of the bat, mitochondria constitute 35% of cytoplasmic volume compared with 29 and 30% in the hamster and rat, respectively. Notably, crista density is much higher in the bat cells (3.58 × 105 cm–1) than in those of the hamster (2.59 × 105 cm–1) and of the rat (2.48 × 105 cm–1). Myofibril concentration is 40% in the bat, 53% in the hamster and 55% in the rat. There is greater numerical density of lipid bodies in the bat (212.27 × 109 cm–3) than in the hamster (139.20 × 109 cm–3) and in the rat (114.00 × 109 cm–3). The volume occupied by T tubules is 0.02 in the bat and hamster, and 0.009 in the rat. These differences suggest structural design for efficient metabolic activity in the bat which, among mammals, has high exercise tolerance.

The inner ear of the sea lamprey, Petromyzon marinus, was examined using scanning and transmission electron microscopy. Many of the nonsensory surfaces of the ear chamber are lined

The central distribution of primary afferent fibers of the eighth cranial nerve was analyzed in the common South American caiman by comparison of patterns of anterograde fiber degeneration resulting from differential lesions of the nerve. Degenerating fibers from the papilla basilaris project only to ipsilateral nuclei angularis, magnocellularis medialis and lateralis, and to the neuropil above laminaris. Discrete electrolytic lesions suggest a spatial ordering of this auditory projection within the ''cochlear'' nuclei. Primary afferents from vestibular endorgans distribute to six nuclei ipsilaterally: ventrolateralis, ventromedialis, descendens, tangentialis, dorsolateralis, and a previously unrecognized group labeled here ''dorsomedialis''. Analysis of differential degeneration patterns indicate that nerves from specific semicircular canals project to restricted regions within the vestibular nuclear complex. For example, the dorsal subdivision of ventrolateralis receives fibers chiefly from the posterior crista, while the anterior and horizontal canal nerves project to the ventral and medial subdivisions. Primary vestibular fibers also project bilaterally to the granular layer of the cerebellum at more rostral levels.

A scanning electron microscope study of corrosion cast preparations of the vessels of the crista ampullaris was carried out in adult rats. This method shows the microvasculature of the cristae in the three-dimensional model. As a result of this technique we have been able to demonstrate on microscopical level a particular microvasculature in the septum cruciatum of the crista in rat.

The general shape of the cupula conformsto the receptor area from which it arises. In the vertical canals of the frog, the cristae have an overall dumbbell shape; the cupula has corresponding enlarged masses which project from the expanded receptor ends while the central portion, which is about one third as thick, completes the diaphragm. The horizontal canal crista has a single enlarged end (club shaped) and consequently has a single cupular mass extending along one side of the ampulla up to the apex. A thinner portion extends to the opposite ampullar wall. In the vertical canals the enlarged masses end before the summit such that the thinner center reaches the apex.The cupula forms a tight diaphragm across the ampulla which is most easily displaced at the center. The central zone of the crista serves to position hair cells about one third the distance to the center of the ampulla while the ends of the crista are more peripherally located in relation to the diaphragm. A graded response to diaphragmatic displacement results. The apex of the cupula is most labile to detachment but not initial displacement. This region can act as a relief valve such that once displacement of the diaphragm has reached its maximum for the base of the cupula, the apical end is displaced and ultimately detached. This mechanism serves to prevent damage to the receptor structure and its cupular relationship.The cupula is composed of two components: filamentous material (protein) and an amorphous substance (mucopolysaccharide). The protein is related to supporting cells and the distal end of the kinocilium. The mucopolysaccharide is secreted from cuboidal cells which surround the receptor area and may serve as a binding substance.From the saddle-shaped receptor surface ciliary tufts consisting of 3 or 4 rows of short stereocilia project into the lumen and a single row of 5 or 6 of these processes continues across the subcupular space (60–70 µm) accompanied by a single kinocilium. The kinocilium continues into the filamentous and mucopolysaccharide matrix of the cupula to form a linkage between the receptor cells and the cupula. Scattered binding filaments are found between the kinocilium and adjacent stereocilia which are similar to those described in the saccule and utricle.

The acousticolateral area of fishes containsa vestibular area and a lateral line area. The vestibular area appears to be very constant with respect to its internal structure, its input, and its relation to the lateral line area. It is more difficult to understand the lateral line area, since this region appears to undergo greater evolutionary modification in various families of fish. The most consistent analysis to date subdivides the acousticolateral area into a nucleus medialis (ant. lobe) and a nucleus dorsalis (post. lobe), but this may be modified when further experimental data becomes available. The vestibulolateral lobe of the cerebellum is, as Larsell already indicated, closely related to the acousticolateral area. This cerebellar region contains an eminentia granulans aligned with the nucleus medialis, and an auricle (lobus caudalis) aligned with the nucleus dorsalis. The molecular layer of the vestibulolateral lobe of the cerebellum continues as the crista cerebellaris of the acousticolateral area; our data for the weakly electric fish indicates that the crista cerebellaris contains: (1) axons of interneurons of the acousticolateral area, and (2) vestibulolateral efferents organized as parallel fibers. Direct afferent input from the lateral line to the crista cerebellaris may be an uncommon specialization.