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Betahistine has been used to treat several vestibular disorders of both central and peripheral origin. The objective of this work was to study the action of betahistine in the vestibular endorgans. Experiments were done in wild larval axolotl (Ambystoma tigrinum). Multiunit extracellular recordings were obtained from the semicircular canal nerve using a suction electrode. Betahistine (10 microM to 10 mM; n = 32) inhibited the basal spike discharge of the vestibular afferent neurons with an IC50 of 600 microM. To define the site of action of betahistine, its interactions with the nitric oxide synthase inhibitor NG-nitro-L-arginine (3 microM) and with the cholinergic antagonists atropine (10 microM; n = 3) and d-tubocurarine (10 microM; n = 3) were studied. The action of betahistine when co-administered with these drugs was the same as that in control experiments, indicating that its effects did not include nitric oxide production or the activation of cholinergic receptors. In contrast, 0.01-1 mM betahistine reduced the excitatory action of kainic acid (10 microM; n = 6) and quiscualic acid (1 microM; n = 13). These results indicate that the action of betahistine on the spike discharge of afferent neurons seems to be due to a post-synaptic inhibitory action on the primary afferent neuron response to the hair cell neurotransmitter.

Morphological and metabolic differences in the otoconia on vestibular dark cells of the ampullar area before and after streptomycin treatment were studied by scanning electron microscopy and X-ray microanalyser. Young adult pigmented guinea pigs were used in this study. In the control group, distribution of the otoconia showed a regular pattern. In the SM group the otoconia decreased in numbers and the regularity of the distribution pattern seemed to disappear. Calcium content of the otoconia in SM group also decreased. From these findings, it was concluded that SM might affect not only the sensory and supporting cells but also the vestibular dark cells.

Human cochlear and vestibular hair cells (HCs) were analysed for the three major cytoskeletal types of structures: microfilaments, microtubules, and intermediate filaments and several of their associated proteins. Specific immunomorphological features were identified: the apical surface, the infracuticular rod of F-actin, the cytoplasm and the HC bases and their interactions with adjacent supporting cells. There is morphological evidence for at least three functionally interacting units: the OHC as a cytoskeletal string interacting with the Deiter's cell, being a part of the rigid pancellular protein shell of the organ of Corti; compartmentalization of HCs (surrounded by rigid intermediate filament proteins in the supporting cells); and a calcium-guided short-loop feed-back control of type I HCs. The cytoskeletal composition of all four types of human HCs and their adjacent structures is similar to, although not identical with, corresponding compositions in other mammalian species.

Many calcitonin gene-related peptide-like immunoreactive (CGRP-IR) fibers were found in the vestibular end-organs and the cochlea of rats. CGRP-IR fibers in the vestibular end-organs originated in the bilateral cell groups dorsolateral to the genu of the facial nerve. These fibers formed a fiber plexus at the base of the sensory epithelia in the maculae of the otolith organs and the ampullae of the semicircular canals, and formed synaptic contacts with the nerve chalice on type I vestibular sensory cells. CGRP-IR fibers in the cochlea originated in the ipsilateral lateral superior olivary nucleus. Most of them existed in the inner spiral bundle under the inner hair cells, and formed synaptic contacts with afferent terminals on the inner hair cells. These findings suggest a postsynaptic modulation of CGRP on the vestibular and cochlear information at the level of type I vestibular sensory cells and the inner hair cells.

Guinea pig cochlear supporting cells have microtubules which are composed of 15, instead of the ordinary 13, protofilaments. The microtubules form a large and stiff bundle involving abundant actin filaments to provide effective rigidity to the cell specialized for transduction of extremely high-frequent mechanical stimuli. We examined microtubules in guinea pig vestibular end organs with the transmission electron microscopy after treatment with tannic acid. Solitary microtubules occurred abundantly in the supranuclear region of type I hair cells, but sparsely in type II hair cells. Individual microtubules consisted of an ordinary set of 13 protofilaments in these hair cells as well as in the supporting cells. Supporting cells were characterized by cytoskeletal bundles of 2 to 30 microtubules which were found to be connected with actin filaments via cross-linking units. Results from the present investigation indicate that such less-organized microtubules of 13 protofilaments are sufficient for vestibular supporting cells which are specialized for detection of lower-frequency vibration together with fellow sensory cells.

Incubation of vestibular ganglion cells from the rat fetus and chick embryos was successfully done demonstrating bipolar cells and two types of multipolar cells, small round cells and large cells, in the cell cultures produced. Vestibular ganglion cells were found to be highly irregular in size. Furthermore, the presence of neurotransmitters (choline acetyltransferase and substance P) was confirmed immunohistochemically. Substance P positive cells had many bipolar cells and some multipolar cells. However, choline acetyl transferase positive cells had some small multipolar cells but few bipolar cells. These findings suggest that all vestibular ganglion cells do not have the same function.

The crista ampullaris, the macula utriculi and the macula sacculi in the waltzing guinea pig were investigated with light microscopy, transmission and scanning electron microscopy. The degenerative changes consist of increasing degrees of apical protrusion of the type I hair cell into the endolymphatic space and of sensory hair fusion. The development of an intracellular actin filament rod in the type I hair cell is coupled to the degenerative changes of the apical part of the cell. Progressive hair cell degeneration with actin rod formation and sensory hair fusion as two important findings in the degenerative pattern is observed in type I hair cells of all sensory areas in the vestibular part of the labyrinth in the waltzing guinea pig. Scanning electron microscopy, shows a concentration of the more advanced stages of degenerative changes to the central part of the crista ampullaris and to the striolar area in the macula utriculi and in the macula sacculi. The fact that there is a concentration of sensory cell damage in the central areas of the vestibular end organs in genetically induced inner ear disease as well as in other inner ear damage supports the concept that the central areas have a different function. This paper further supports earlier suggestions that the type I and type II hair cells are genetically different cell types having different functions.

The present experiment was designed to determine which neurotransmitter influences the burst pattern in the firing of the inhibitory burst neurons (IBN) during vestibular nystagmus. Cats were anesthetized with ether and mounted in a stereotaxic apparatus on a turntable, implanted stimulation electrodes, removed occipital bone and aspirated the vermal part of cerebellum. After the operation ether was discontinued. The recordings took place with the cats in an alert condition created by upper cervical cord transsection, artificial respiration and local anesthesia by infiltrating 0.5% lidocaine into the semilunar ganglions every two hours. We also employed iontophoretic application of the various drugs: GABA, muscimol, glycine, serotonin (5-HT) and bicuculline through seven-barrelled glass micropipettes. GABA or muscimol did not influence nystagmus rhythm, but both chemicals caused strong suppression of burst activities in IBN. Since this inhibitory effect of GABA was suppressed by the simultaneous application of bicuculline, IBNs appear to be controlled by GABAA receptor. Glycine and 5-HT did not change the firing pattern of IBN. Application of bicuculline itself caused an increase of tonic discharges of IBN. These findings suggest that IBN receive inhibitory impulses from the higher GABAergic neurons.

In decerebrate cats we used response dynamics to classify neurons in Deiters' nucleus and the rostral descending nucleus as receiving input from vertical canals, otolith organs (utricle) or canal + otolith. Many of these neurons, particularly those with convergent vestibular input (canal + otolith, canal + canal) and preferred stimulus directions near roll, also received neck input. Neck and vestibular response vectors tended to point in opposite directions. Neck and vestibular response dynamics were often well matched, so that combined stimuli (head rotation) produced no response over a wide frequency range. In some cases differing dynamics produced an output that appeared to code head position.