Bilateral otolith contribution to spatial coding in the vestibular system

Recent work on the coding of spatial information in central otolith neurons has significantly advanced our knowledge of signal transformation from head-fixed otolith coordinates to space-centered coordinates during motion. In this review, emphasis is placed on the neural mechanisms by which signals generated at the bilateral labyrinths are recognized as gravity-dependent spatial information and in turn as substrate for otolithic reflexes. We first focus on the spatiotemporal neuronal response patterns (i.e. one- and two-dimensional neurons) to pure otolith stimulation, as assessed by single unit recording from the vestibular nucleus in labyrinth-intact animals. These spatiotemporal features are also analyzed in association with other electrophysiological properties to evaluate their role in the central construction of a spatial frame of reference in the otolith system. Data derived from animals with elimination of inputs from one labyrinth then provide evidence that during vestibular stimulation signals arising from a single utricle are operative at the level of both the ipsilateral and contralateral vestibular nuclei. Hemilabyrinthectomy also revealed neural asymmetries in spontaneous activity, response dynamics and spatial coding behavior between neuronal subpopulations on the two sides and as a result suggested a segregation of otolith signals reaching the ipsilateral and contralateral vestibular nuclei. Recent studies have confirmed and extended previous observations that the recovery of resting activity within the vestibular nuclear complex during vestibular compensation is related to changes in both intrinsic membrane properties and capacities to respond to extracellular factors. The bilateral imbalance provides the basis for deranged spatial coding and motor deficits accompanying hemilabyrinthectomy. Taken together, these experimental findings indicate that in the normal state converging inputs from bilateral vestibular labyrinths are essential to spatiotemporal signal transformation at the central otolith neurons during low-frequency head movements.     

Physical dimensions influence the functional property of the semicircular canal

The functional dependence of the semicircular canal upon its physical dimensions was evaluated by measuring the internal radius (r), the radius of curvature (R) and the cupula radius (rC) of the posterior canal in 10 freshly dissected frog labyrinths. These values have been compared to the same parameters of the cat labyrinth. The coefficients I, B, K in the Steinhausen equation were determined for both animals. The A ratio between cupula deflection and endolymph displacement was also calculated by utilizing the Bernard equation. The A ratio is three times larger in the frog than in the cat. It follows that if the same acceleration produces similar endolymph displacements in the posterior canal of both animals, the cupula deflection will be larger in the frog. The solution of the Steinhausen equation in the presence of a constant acceleration, however, reveals that the same stimulus intensity will result in a larger endolymph displacement in the cat posterior canal; similarly, the endolymph displacement directly depends on the duration of the stimulating period in both animals. Contrary to the Bernard assumption, these effects generate a G ratio (psi frog/psi cat) which is less than the Q ratio (A frog/A cat). Moreover, G decreases on increasing the duration of the stimulating period. For stimuli of short duration the semicircular canal of a small animal is expected to exhibit a higher sensitivity than that of a larger one. However, the definitive primary afferent discharge will be largely controlled by the receptor/generator potential properties.     

Stimulus dependence of the development of the zebrafish (Danio rerio) vestibular system

ABSTRACT: It has been suggested that stimulus dependence is a general feature of all developing sensory systems. We tested this idea for the developing zebrafish vestibular system using a bioreactor the National Aeronautic and Space Agency designed to simulate microgravity for cells in culture on earth. We replaced the culture medium with aquarium water and maintained zebrafish eggs/hatchlings in the bioreactor for either 72 or 96 h postfertilization. These experimental animals displayed a swimming behavior that was indistinguishable from the control animals when illuminated from above. However, when illuminated from below, experimental animals swam not only dorsal surface up, but also lying on their side; they corkscrewed, swam vertical loops, and occasionally even swam upside down. When incubated in the bioreactor for 96 h, the saccular otolith was significantly smaller than normal, suggesting that otolith development was either delayed or slower than normal. When incubated in the bioreactor for 72 h, some animals were missing one or more otoliths. In contrast, control animals all had two otoliths on each side. This supports the idea that otolith development was delayed. Immediately upon removal from the bioreactor at 96 h, experimental animals showed some signs of compensatory eye rotation, but with a much less clear relationship between the orientation of the eye and the direction of gravity than the age-matched control animals. This difference was still obvious 1 day later. These results support the idea that development of the vestibular system in zebrafish is dependent on the presence of the normal stimulus the system is designed to detect.     

On the problem of cooperation of the reactions of hands: III. Cooperation of hand reactions to auditory and visual stimuli in patients with focal lesions of the brainstem and diencephalon

The response time (simple mental reaction time) cooperation was estimated in 53 patients with focal lesions of the brainstem and diencephalon (thalamus). The cooperation between the left-and right-hand simple mental reactions to auditory and visual stimuli presented after a warning stimulus was analyzed to determine the morphological structures responsible for the cooperation of responses. The cooperation of the simple mental reaction remained normal in some of the subjects and was disturbed in others. In the latter case, the correlation coefficient between the left-and right-hand simple mental reactions to an auditory or visual stimulus or both stimuli simultaneously was changed. The disturbances were detected in patients with lesions of the tectum at the boundary between the medulla and the pons and in those with affected lateral regions of the thalamus.     

Adrenergic control of cardian pacemaker currents.

Pacemaker activity in atrial muscle and in Purkinje fibres is generated by a time-dependent decay of potassium current that allows the membrane to be depolarized to the threshold for action potential initiation. The kinetics of the pacemaker potassium currents in these two parts of the heart are sufficiently different to indicate that they correspond to different membrane structures. This conclusion is strengthened by the discovery that the mechanisms of acceleration produced by adrenaline are also quite different. In Purkinje fibres, the activation threshold for the potassium current is shifted in a depolarizing direction with no change in maximum amplitude. This voltage shift is adequate by itself to explain the acceleration. In atrial fibres the pacemaker potassium current is increased in amplitude with no shift in threshold. By itself, this action of adrenaline would slow pacemaker activity and the acceleration in this case is dependent on a large increase in the current attributable to calcium ions. The roles of cyclic 3',5'-AMP and of intracellular calcium ions in mediating the pacemaker actions of adrenaline will also be discussed.     

Localization of beta-glycerophosphatase and Mg++-activated adenosine triphosphatase in a moss haustorium,and the relation of these enzymes to the cell wall labyrinth

Summary Acid phosphatase and ATPase were localized in the bryophyte haustorium and in the surrounding paternal tissue of the gametophyte. Only cells with wall labyrinths are the sites of intense enzyme activity.The reaction products of both enzymes were found to occur in cell organelles, the plasma membrane and particularly in wall inclusions that are supposedly proteinaceous in nature.The intensity of the reaction is proportional to the state of differentiation of the labyrinth. The highest enzyme activity was encountered in the epidermal cells which are furnished with the most elaborate wall labyrinths. Somewhat lower was the activity in the other labyrinth cells with filiform ingrowths.These findings stress the role of the epidermis as an absorptive epithelium, and also show clearly that the enzyme activity associated with the plasma surface is in no reciprocal ratio to the degree of amplification of the surface area.     

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/sec², 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/sec².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.     

Tuning of the ocular vestibular evoked myogenic potential to bone-conducted sound stimulation

Ocular vestibular evoked myogenic potentials (oVEMPs) are a recently described clinical measure of the vestibulo-ocular reflex. Studies demonstrating differences in frequency tuning between air-conducted and bone-conducted (BC) oVEMPs suggest a separate vestibular (otolith) origin for each stimulus modality. In this study, 10 healthy subjects were stimulated with BC stimuli using a hand-held minishaker. Frequencies were tested in the range of 50-1,000 Hz using both a constant-force and constant-acceleration method. Subjects were stimulated at the mastoid process and the forehead. For constant-force stimulation at both sites, maximum acceleration occurred around 100 Hz, in differing axes. Both forms of stimulation had low-frequency peaks of oVEMP amplitudes (constant force: mastoid, 80-150 Hz; forehead, 50-125 Hz; constant acceleration: mastoid, 100-200 Hz; forehead, 80-150 Hz), for both sites of application, despite differences in the magnitude and direction of evoked head acceleration. For mastoid stimulation, ocular responses changed from out of phase to in phase for 400 Hz and above. Our results demonstrate that BC stimuli show tuning around 100 Hz, independent of stimulus site, that is not due to skull properties. The findings are consistent with an effect on a receptor with a resonance around 100 Hz, most likely the utricle.     

The endocytosis of asbestos by mouse peritoneal macrophages and its long-term effect on iron accumulation and labyrinth formation

The effect of a single intraperitoneal injection of crocidolite asbestos fibres on the peritoneal cell population were studied. Attention was paid to the changes in the proportions taken by the various types of cell in this population after peritoneal stimulation as well as the handling of asbestos fibres by the peritoneal cells and the formation of asbestos bodies. Intraperitoneal administration of crocidolite led to an influx of inflammatory cells into the peritoneal cavity. The asbestos fibres were phagocytosed and gradually cleared from the peritoneal cavity. Long before this clearance was completed, the peritoneal cell population had returned to the steady state. The stimulated peritoneal macrophages showed increasing concentrations of iron in both lysosomes and the cytoplasm. At later time points, residual bodies containing iron and asbestos fibres were seen frequently in macrophages, but asbestos bodies were not found. As a reaction to the administration of crocidolite asbestos, macrophages from the peritoneal cavity develop tubular systems (labyrinths) that increase in number and size.     

Development of the interhemispheric response in rats.

In acute experiments on curarized rats, an interhemispheric response was observed for the first time at the age of 5 days. A stimulus of threshold intensity evoked both components of the response in the youngest animals, but only the negative phase of the evoked potential from the 9th day of age, with the initial positive phase appearing only after stimuli of high intensity. Upon using stimuli of double the value of threshold intensity, the responses had the same shape, i.e. positive-negative throughout the whole development. Marked changes in the latency of both components of the response were found during development. Up to 14 days latencies decreased rapidly; this was followed by a phase of relative stability and then, after the 19th day, by further, less pronounced decrease. An after-discharge, a late component of the response in adult animals, appeared for the first time in a mature form at 18 days. An after-discharge of a different shape was seen in young rats aged 7-14 days and none at all was observed in 5-day-old animals.     

Effect of vestibular,somatic, and autonomic afferent impulsation on vestibular nuclear unit activity in cats

Single unit responses in nuclei of the vestibular complex to stimulation of the labyrinths and of proprioceptive and autonomic afferents were investigated. Different types of unit responses were obtained to stimulation, including evoked activity consisting of a group of action potentials followed by inhibition of the spike discharge. Unit activity in the vestibular nuclei was shown to depend on extralabyrinthine stimulation. In response to adequate stimulation of the labyrinths by tilting the head, the role of receptors of muscles and joints in the neck was distinguished. The question of the somatotopic organization of the vestibular nuclei and convergence of various afferent flows on neurons giving rise to the vestibulospinal tract is discussed.Institute of Medico-Biological Problems, Ministry of Health of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 8, No. 5, pp. 507–513, September–October, 1976.     

Short and middle latency vestibular evoked responses to acceleration in man

We have succeeded in recording short and middle latency vestibular evoked responses in human subjects. The head was held rigidly in a special, patented head holder, constructed individually for each subject, which gripped the teeth of the upper jaw. The stimulus consisted of 2/sec steps of angular acceleration impulses produced by a special motor with intensities of about 10,000°/sec² and with a rise time of 1–2 msec. The electrical activity was recorded as the potential difference between special forehead and mastoid electrodes having a large, secure contact area with the skin. The activity was digitally filtered and averaged in 2 separate channels by means of a Microshev 2000 evoked response system. The short latency responses, with peaks at about 3.5 msec (forehead positive), 6.0 msec (forehead negative) and 8.4 msec (forehead positive; bandpass: 200–2000 Hz; average of 1024 trials), had amplitudes of about 0.5 μV. The middle latency responses had peaks at about 8.8 msec (forehead positive), 18.8 msec (forehead negative) and 26.8 msec (forehead positive; 30–300 Hz; N = 128 trials), with larger amplitudes (about 15 μV). These responses were consistently recorded in the same subject at different times and were similar in different normal subjects. Strenuous control experiments were conducted in order to ensure that these responses are not artefacts due to the movement of conducting media (head, electrodes and leads) in the electromagnetic field of the motor and are elicited by activation of normal labyrinths. Among other controls, they were not present in a cadaver, in patients with bilateral absence of nystagmus to caloric stimuli and in conducting volumes the size of the human head. They were also not masked by white noise.     

Brain activation by photic stimulation in normal cats and after transection of afferent pathways to the mesencephalic reticular formation

In chronic experiments on waking, unimmobilized cats with implanted electrodes, the EEG activation reaction evoked by short flashes of varied intensity was recorded in normal animals and after blocking excitatory influences of the visual sensory system on the brain-stem reticular formation by transection of the brachium colliculi superioris bilaterally. The intensity of the activation reaction in intact animals increased steadily with an increase in intensity of the photic stimuli. No clear dependence of response amplitude on stimulus intensity was observed in the cats with transection; the changes were largely random in character. It is suggested that these disturbances were due to interruption both of the ascending flow excitatory afferent impulses to the brain-stem reticular formation through the brachia and superior colliculi and of corticofugal volleys descending from the cortex to the mesencephalic reticular formation via the same brachia, and controlling the level of its activation.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 13, No. 5, pp. 500–505, September–October, 1981.     

Spectrum analysis of vestibular nystagmus

A procedure for the spectral analysis of nystagmograms obtained by rotary stimulation with the rate of 180 degrees/s for 20 s has been developed with the aim to reveal the most typical changes in the vestibular nystagmus with one or another form of the cochleovestibular pathology. A signal recorded in the analogous form was processed by computer EC-1022. Periodograms were calculated by the method of the fast Fourier transform and periodogram smoothing by averaging of realization sites. In case of Ménière's disease the third harmonic was not recorded on periodograms when right and left labyrinths were stimulated and in the case of neurites of acoustic nerves, the third or fifth harmonic was not observed. A supposition is advanced that the third harmonic reflects the state of the peripheral area of the vestibular analyzer, while the fifth harmonic--the central one.     

Processing of hierarchic stimulus structures has advantages in humans and animals

Carmesin and Schwegler (1994) have determined theoretically that a linear hierarchical stimulus structure can be encoded by a parallel network of minimal complexity. The experiments reported here compare the efficiency with which humans and pigeons process sets of stimulus pairs embodying different inequality structures. Groups of subjects of each species were taught to discriminate all 10 pairwise combinations of 5 stimuli with an operant conditioning method. For one group, the reward/punishment allocations within the pairs agreed with a linear hierarchy. For a second and third group, the reinforcement allocations of one or three, respectively, of the stimulus pairs deviated from such ordering. The time it took the subjects to learn the tasks as well as the final choice latencies and/or error rates increased with the number of deviating inequalities. The results agree with the assumption that both humans and pigeons encode stimulus inequality structures with parallel processing neural networks rather than with a sequentially processing algorithm.     

The optic lobes of Lepidoptera

Variants of the Golgi-Colonnier (1964) selective silver procedure have been used to show up neurons in insect brains. Neural elements are particularly clearly impregnated in the optic lobes. Three classes of nerve cells can be distinguished; perpendicular (class I), tangential (class II) and amacrine cells (class III). There are many types of neurons in each class which together have a very wide variety of form. Their components are related to specific strata in the optic lobe regions. Short visual cells from the retina terminate in the lamina in discrete groups of endings (optic cartridges). Pairs of long visual fibres from ommatidia pass through the lamina and end in the medulla. Class I cells link these two regions in parallel with the long visual fibres and groups of these elements define columns in the medulla. These in turn give rise to small-field fibres that project to the lobula complex. Tangential processes intersect the parallel arrays of class I cells at characteristic levels. Some are complex in form and may invade up to three regions. Another type provides a direct link between the ipsi- and contralateral optic lobe. Amacrine cells are intrinsic to single lobe regions and have processes situated at the same levels as those of classes I and II cells. A fifth optic lobe region, the optic tubercle, is connected to the medulla and lobula and also receives a set of processes from the mid-brain. There are at least six separate types of small-field relays which could represent the retina mosaic arrangement in the lobula.     

Effects of linear acceleration on fish behavior and eye movements.

Behavioral responses and eye movements of fish during linear acceleration were reviewed. It is known that displacement of otoliths in the inner ear leads to body movements and/or eye movements. On the ground, the utriculus of the vestibular system is stimulated by otolith displacement caused by gravitational and inertial forces during horizontal acceleration of whole body. When the acceleration is imposed on the fish's longitudinal axis, the fish showed nose-down and nose-up posture for tailward and noseward displacement of otolith respectively. These responses were understood that the fish aligned his longitudinal body axis in a plane perpendicular to the direction of resultant force vector acting on the otoliths. When the acceleration was sideward, the fish rolled around his longitudinal body axis so that his back was tilted against the direction in which the inertial force acted on the otoliths. Linear acceleration applied to fish's longitudinal body axis evoked torsional eye movement. Direction of torsion coincided with the direction of acceleration, which compensate the change of resultant force vector produced by linear acceleration and gravity. Torsional movement of left and right eye coordinated with each other. In normal fish, both sinusoidal and rectangular acceleration of 0.1G could evoke clear eye torsion. Though the amplitude of response increased with increasing magnitude of acceleration up to 0.5 G, the torsion angle did not fully compensate the angle calculated from gravity and linear acceleration. Removal of the otolith on one side reduced the response amplitude of both eyes. The torsion angle evoked by rectangular acceleration was smaller than that evoked by sinusoidal acceleration in both normal and unilaterally labyrinthectomized fish. These results suggest that eye torsion of fish include both static and dynamic components.     

Stabilometry and definition of the threshold of galvanic vestibular stimulation in normal subjects: an experimental study

The effect of the galvanic stimulation on the vestibular apparatus has been evaluated by registration on the postural deviations, using a stabilometry platform. We have studied the galvanic body-sway responses in a group of normal subjects, using a binauricolar bipolar stimulation, with the electrodes attached by means of surgical tape to the mastoid area. The records of body-sway responses have demonstrated in 80% of the considered cases a significant variation of all positional parameters after a current intensity of 2 mA, according the body sways toward the positive stimulus. At the same current intensity only five of the studied subjects have shown multidirectional swinging, in three cases joined with a subjective slight sway toward the ear stimulated with positive polarity. Therefore the galvanic test, joined with the posturography, proves to be a useful auxiliary method in vestibular investigation, allowing us to lower the threshold of galvanic stimulation and to make the electric stimulus better supported for the patient.     

Activation changes in zebra finch (Taeniopygia guttata) brain areas evoked by alterations of the earth magnetic field

Many animals are able to perceive the earth magnetic field and to use it for orientation and navigation within the environment. The mechanisms underlying the perception and processing of magnetic field information within the brain have been thoroughly studied, especially in birds, but are still obscure. Three hypotheses are currently discussed, dealing with ferromagnetic particles in the beak of birds, with the same sort of particles within the lagena organs, or describing magnetically influenced radical-pair processes within retinal photopigments. Each hypothesis is related to a well-known sensory organ and claims parallel processing of magnetic field information with somatosensory, vestibular and visual input, respectively. Changes in activation within nuclei of the respective sensory systems have been shown previously. Most of these previous experiments employed intensity enhanced magnetic stimuli or lesions. We here exposed unrestrained zebra finches to either a stationary or a rotating magnetic field of the local intensity and inclination. C-Fos was used as an activity marker to examine whether the two treatments led to differences in fourteen brain areas including nuclei of the somatosensory, vestibular and visual system. An ANOVA revealed an overall effect of treatment, indicating that the magnetic field change was perceived by the birds. While the differences were too small to be significant in most areas, a significant enhancement of activation by the rotating stimulus was found in a hippocampal subdivision. Part of the hyperpallium showed a strong, nearly significant, increase. Our results are compatible with previous studies demonstrating an involvement of at least three different sensory systems in earth magnetic field perception and suggest that these systems, probably less elaborated, may also be found in nonmigrating birds.     

Changes in early acoustic-evoked potentials by mildly arousing priming stimuli in carp (Cyprinus carpio).

1. Averaged acoustic-evoked potential (AEPs) in the medulla and midbrain were recorded, as were changes in heart rate, indicating arousal, to a previous non-acoustic priming stimulus. 2. Useful AEP measures were amplitude of the early biphasic wave (less than 10 msec) in medulla and amplitude and duration of this wave in midbrain. 3. There was a negative regression of heart rate and medullary AEP amplitude especially evident for a 2 sec light stimulus. Decreased AEP amplitude in both regions was induced by water movement and an increase in midbrain AEP duration by the tactile stimulus. 4. Arousal effects even on these early AEP measures are specific to the form of arousing stimulus.