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At least 19 recordsLinked to original sources
PubMed1989

Studies of the horizontal vestibulo-ocular reflex in spaceflight.

Changes in the vestibulo-ocular reflex (VOR) during space flight have been suspected of contributing to space motion sickness. The horizontal VOR was studied in nine subjects on two space shuttle missions. Active unpaced head oscillation at 0.3 Hz was used as the stimulus to examine the gain and phase of the VOR with and without visual input, as well as the visual suppression of the reflex. No statistically significant changes were noted inflight in the gains or phase shifts of the VOR during any test condition, or between space motion sickness susceptible and nonsusceptible populations. Although VOR suppression was unaffected by spaceflight, the space motion sickness-susceptible group tended to exhibit greater error in the suppression than the nonsusceptible group. It is concluded that at this stimulus frequency, VOR gain is unaffected by spaceflight, and any minor individual changes do not seem to contribute to space motion sickness.

Adult↗
PubMed1991

Human vestibular function and weightlessness.

This article presents the concept of a spatial orientation/motion perceptual system, the contributions of the vestibular receptors to this system, and apparatus and training procedures and observations to allow astronauts to preadapt to weightlessness. The author also discusses perceptual reactions to prolonged weightlessness.

Adaptation, Physiological↗
PubMed1991

New pharmacologic approaches to the prevention of space/motion sickness.

Fundamental approaches in selection of new agents for evaluation in prevention of space/motion sickness (SMS) are reviewed. The discussion centers on drugs under investigation at the Johnson Space Center. Methodology that employs the rotating chair for measuring SMS symptomatology and susceptibility is described. The most obvious approach to the development of new agents relies on selection of agents from drug classes that possess pharmacologic properties of established anti-motion sickness agents. A second approach selects drugs that are used to prevent emesis caused by means other than exposure to motion. The third approach relies on basic research that characterizes individual differences in susceptibility. The hypothesis is: detection of individual differences leads to identification of specific drugs, which target physiologic systems that show individual differences. These physiologic systems are targets for therapy and may play a role in the etiology of SMS. Two drugs that reduce susceptibility to SMS include dexamethasone and d(CH2)5Tyr(Me)AVP, a vasopressin (AVP)V1 antagonist. The latter peptide has demonstrated complete blockade of emesis and other significant symptoms in squirrel monkeys. These studies were predicated on observations that subjects who were more resistant to SMS had higher plasma AVP after severe nausea than subjects with lower resistances. Investigations are underway to test a 0.5-mg intravenous dose in humans. Kappa opioid agonists inhibit AVP release and offer new therapeutic possibilities and advantages over AVP peptides. This review details the experimental data collected on AVP and adrenocorticotropin. The literature supports interrelated roles for AVP and opioid peptides in SMS. Experimental testing of kappa agonists is warranted because specific opioid agonists act at neuroanatomical sites causing nausea and vomiting. It is argued opioid receptors in the chemoreceptor trigger zone and vomiting center stimulate and inhibit the emetic response, respectively. The evidence suggests kappa and/or mu receptors at VC are involved in inhibition of emesis, whereas delta opioid receptors at CTZ are involved in stimulation of emesis.

Drug Therapy↗
PubMed1993

High resolution and image processing of otoconia matrix.

This study was designed to investigate patterns of fibrils organization in histochemically stained otoconia. Transmission electron microscope and video imaging were used. These data indicate that otoconia of the chick (Gallus domesticus) inner ear may have central cores in vivo. The data also show that the ultrastructural organization of fibrils fixed with aldehydes and histochemical stains follows trajectories that conform to the hexagonal shape of otoconia. These changes in direction may contribute to the formation of a central core. The existence of central cores is important for the in vivo buoyancy of otoconia. Packing of fibrils is tighter after phosphotungstic acid (PTA) stained otoconia than with other histochemical stains, which usually produce looser packing of fibrils and seemingly larger central core. TEM of tilted and untilted material showed that turning of fibrils occurs at the points where the face angles of otoconia form and where central cores exist. Video image processing of the images allowed reconstructing a template which, if assumed to repeat and change trajectories, would fit the pattern of fibrils seen in fixed otoconia. Since it is highly unlikely that aldehyde primary fixation or PTA stain caused such drastic change in the direction of fibrils, the template derived from these results may closely approximate patterns of otoconia fibrils packing in vivo. However, if the above is correct, the perfect crystallographic diffraction pattern of unfixed otoconia do not correspond to patterns of fixed fibrils.

Animals↗
PubMed1995

Carbonic anhydrase is required for statoconia homeostasis in organ cultures of statocysts from Aplysia californica.

A novel organ culture system has been developed to study the regulation of statoconia production in the gravity sensing organ in Aplysia californica. Statocysts were cultured in Leibovitz (L15) medium supplemented with salts and Aplysia haemolymph for four days at 17 degrees C. The viability of the system was evaluated by examining four parameters: statocyst morphology, the activity of the mechanosensory cilia in the statocyst, production of new statoconia during culture and change in statoconia volume after culture. There were no morphological differences in statocysts before and after culture when ciliary beating was maintained. There was a 29% increase in the number of statoconia after four days in culture. Mean statocyst, statolith and statoconia volumes were not affected by culture conditions. The presence of carbonic anhydrase in the statocysts was shown using immunohistochemistry. When statocysts were cultured in the presence of 4.0 x 10(-4) M acetazolamide to inhibit the enzyme activity, there was a decrease in statoconia production and statoconia volume, indicating a role for this enzyme in statoconia homeostasis, potentially via pH regulation. These studies are the first to report a novel system for the culture of statocysts and show that carbonic anhydrase is involved in the regulation of statoconia volume and production.

Animals↗
PubMed1996

Lower limb kinematics during treadmill walking after space flight: implications for gaze stabilization.

We examined the lower limb joint kinematics observed during pre- and postflight treadmill walking performed by seven subjects from three Space Shuttle flights flown between March 1992 and February 1994. Basic temporal characteristics of the gait patterns, such as stride time and duty cycle, showed no significant changes after flight. Evaluation of phaseplane variability across the gait cycle suggests that postflight treadmill walking is more variable than preflight, but the response throughout the course of a cycle is joint dependent and, furthermore, the changes are subject dependent. However, analysis of the phaseplane variability at the specific locomotor events of heel strike and toe off indicated statistically significant postflight increases in knee variability at the moment of heel strike and significantly higher postflight hip joint variability at the moment of toe off. Nevertheless, the observation of component-specific variability was not sufficient to cause a change in the overall lower limb joint system stability, since there was no significant change in an index used to evaluate this at both toe off and heel strike. The implications of the observed lower limb kinematics for head and gaze control during locomotion are discussed in light of a hypothesized change in the energy attenuation capacity of the musculoskeletal system in adapting to weightlessness.

Adult↗
PubMed1995

The effects of spaceflight on open-loop and closed-loop postural control mechanisms: human neurovestibular studies on SLS-2.

Stabilogram-diffusion analysis was used to examine how prolonged periods in microgravity affect the open-loop and closed-loop postural control mechanisms. It was hypothesized that following spaceflight: (1) the effective stochastic activity of the open-loop postural control schemes in astronauts is increased; (2) the effective stochastic activity and uncorrelated behavior, respectively, of the closed-loop postural control mechanisms in astronauts are increased; and (3) astronauts utilized open-loop postural controls schemes for shorter time intervals and smaller displacements. Four crew members and two alternates from the 14-day Spacelab Life Sciences 2 Mission were included in the study. Each subject was tested under eyes-open, quiet-standing conditions on multiple preflight and postflight days. The subjects' center-of-pressure trajectories were measured with a force platform and analyzed according to stabilogram-diffusion analysis. It was found that the effective stochastic activity of the open-loop postural control schemes in three of the four crew members was increased following spaceflight. This result is interpreted as an indication that there may be in-flight adaptations to higher-level descending postural control pathways, e.g., a postflight increase in the tonic activation of postural muscles. This change may also be the consequence of a compensatory (e.g., "stiffening") postural control strategy that is adopted by astronauts to account for general feeling of postflight unsteadiness. The crew members, as a group, did not exhibit any consistent preflight/postflight differences in the steady-state behavior of their closed-loop postural control mechanisms or in the functional interaction of their open-loop and closed-loop postural control mechanisms. These results are interpreted as indications that although there may be in-flight adaptations to the vestibular system and/or proprioceptive system, input from the visual system can compensate for such changes during undisturbed stance.

Humans↗
PubMed1996

The dynamic contributions of the otolith organs to human ocular torsion.

We measured human ocular torsion (OT) monocularly (using video) and binocularly (using search coils) while sinusoidally accelerating (0.7 g) five human subjects along an earth-horizontal axis at five frequencies (0.35, 0.4, 0.5, 0.75, and 1.0 Hz). The compensatory nature of OT was investigated by changing the relative orientation of the dynamic (linear acceleration) and static (gravitational) cues. Four subject orientations were investigated: (1) Y-upright-acceleration along the interaural (y) axis while upright; (2) Y-supine-acceleration along the y-axis while supine; (3) Z-RED-acceleration along the dorsoventral (z) axis with right ear down; (4) Z-supine-acceleration along the z-axis while supine. Linear acceleration in the Y-upright, Y-supine and Z-RED orientations elicited conjugate OT. The smaller response in the Z-supine orientation appeared disconjugate. The amplitude of the response decreased and the phase lag increased with increasing frequency for each orientation. This frequency dependence does not match the frequency response of the regular or irregular afferent otolith neurons; therefore the response dynamics cannot be explained by simple peripheral mechanisms. The Y-upright responses were larger than the Y-supine responses (P < 0.05). This difference indicates that OT must be more complicated than a simple low-pass filtered response to interaural shear force, since the dynamic shear force along the interaural axis was identical in these two orientations. The Y-supine responses were, in turn, larger than the Z-RED responses (P < 0.01). Interestingly, the vector sum of the Y-supine responses plus Z-RED responses was not significantly different (P = 0.99) from the Y-upright responses. This suggests that, in this frequency range, the conjugate OT response during Y-upright stimulation might be composed of two components: (1) a response to shear force along the y-axis (as in Y-supine stimulation), and (2) a response to roll tilt of gravitoinertial force (as in Z-RED stimulation).

Acceleration↗
PubMed1996

Spatial orientation of semicircular canals and afferent sensitivity vectors in pigeons.

Rotational head motion in vertebrates is detected by the semicircular canal system, whose innervating primary afferent fibers carry information about movement in specific head planes. The semicircular canals have been qualitatively examined over a number of years, and the canal planes have been quantitatively characterized in several animal species. The present study first determined the geometric relationship between individual semicircular canals and between the canals and the stereotactic head planes in pigeons. Stereotactic measurements of multiple points along the circumference of the bony canals were taken, and the measured points fitted with a three-dimensional planar surface. Direction normals to the plane's surface were calculated and used to define angles between semicircular canal pairs. Because of the unusual shape of the anterior semicircular canals in pigeons, two planes, a major and a minor, were fitted to the canal's course. Calculated angle values for all canals indicated that the horizontal and posterior semicircular canals are nearly orthogonal, but the anterior canals have substantial deviations from orthogonality with other canal planes. Next, the responses of the afferent fibers that innervate each of the semicircular canals to 0.5 Hz sinusoidal rotation about an earth-vertical axis were obtained. The head orientation relative to the rotation axis was systematically varied so that directions of maximum sensitivity for each canal afferent could be determined. These sensitivity vectors were then compared with the canal plane direction normals. The afferents that innervated specific semicircular canals formed homogeneous clusters of sensitivity vectors in different head planes. The horizontal and posterior afferents had average sensitivity vectors that were largely co-incident with the innervated canal plane direction normals. Anterior canal afferents, however, appeared to synthesize contributions from the major and minor plane components of the bony canal structure to produce a resultant sensitivity vector that was positioned between the canal planes. Calculated angles between the average canal afferent sensitivity vectors revealed that direction orthogonality is preserved at the afferent signal level, even though deviations from canal plane orthogonality exist.

Afferent Pathways↗
PubMed1996

Modulation of vergence by off-vertical yaw axis rotation in the monkey: normal characteristics and effects of space flight.

Horizontal movements of both eyes were recorded simultaneously using scleral search coils in 2 rhesus monkeys before and after the COSMOS 2229 space-flight of 1992-1993. Another 9 monkeys were tested at comparable time intervals and served as controls. Ocular vergence, defined as the difference in horizontal position between the left and right eyes, was measured during off-vertical yaw axis rotation (OVAR) in darkness. Vergence was modulated sinusoidally as a function of head position with regard to gravity during OVAR. The amplitude of peak-to-peak modulation increased with increments in tilt of the angle of the rotational axis (OVAR tilt angle) that ranged from 15 degrees to 90 degrees. Of the 11 monkeys tested, 1 had no measurable modulation in vergence. In the other 10, the mean amplitude of the peak to peak modulation was 5.5 degrees +/- 1.3 degrees at 90 degrees tilt. Each of these monkeys had maximal vergence when its nose was pointed close to upward (gravity back; mean phase: -0.9 degree +/- 26 degrees). After space flight, the modulation in vergence was reduced by over 50% for the two flight monkeys, but the phase of vergence modulation was not altered. The reduction in vergence modulation was sustained for the 11-day postflight testing period. We conclude that changes in vergence are induced in monkeys by the sinusoidal component of gravity acting along the naso-occipital axis during yaw axis OVAR, and that the modulation of the vergence reflex is significantly less sensitive to linear acceleration after space flight.

Animals↗
PubMed1996

The delayed rectifier, IKI, is the major conductance in type I vestibular hair cells across vestibular end organs.

Hair cells were dissociated from the semicircular canal, utricle, lagena and saccule of white king pigeons. Type I hair cells were identified morphologically based on the ratios of neck width to cuticular plate width (NPR < 0.72) as well as neck width to cell body width (NBR < 0.64). The perforated patch variant of the whole-cell recording technique was used to measure electrical properties from type I hair cells. In voltage-clamp, the membrane properties of all identified type I cells were dominated by a predominantly outward potassium current, previously characterized in semicircular canal as IKI. Zero-current potential, activation, deactivation, slope conductance, pharmacologic and steady-state properties of the complex currents were not statistically different between type I hair cells of different vestibular end organs. The voltage dependence causes a significant proportion of this conductance to be active about the cell's zero-current potential. The first report of the whole-cell activation kinetics of the conductance is presented, showing a voltage dependence that could be best fit by an equation for a single exponential. Results presented here are the first data from pigeon dissociated type I hair cells from utricle, saccule and lagena suggesting that the basolateral conductances of a morphologically identified population of type I hair cells are conserved between functionally different vestibular end organs; the major conductance being a delayed rectifier characterized previously in semicircular canal hair cells as IKI.

4-Aminopyridine↗
PubMed1996

On the origin of eye movement desensitization and reprocessing: a response to Rosen.

Rosen argues that the eye movements experienced by Shapiro during the incident leading to her development of eye movement desensitization and reprocessing (EMDR) could not, as she later inferred, have been saccadic. The present author disputes Rosen's conclusion by showing that his arguments are based on a faulty understanding of the nature of saccadic eye movements or are irrelevant to Shapiro's claim.

Attention↗
PubMed1995

Functional support of glutamate as a vestibular hair cell transmitter in an amniote.

Although hair cells in the cochlea and in the vestibular endorgans of anamniotes are thought to release glutamate or a similar compound as their transmitter, there is little evidence in amniotes (which, unlike anamniotes, possess both type I and II hair cells) as to the nature of the hair cell transmitters in the vestibular labyrinth. We have recorded extracellularly from single semicircular canal afferents in the turtle labyrinth maintained in vitro and have bath-applied a number of transmitter agonists and antagonists to relate the effects of these substances to the actions of the endogenous transmitter substances. Both glutamate and aspartate strongly excite the afferents while GABA and carbachol have negligible or weak effects. In contrast to its lack of effect on afferent activity in some anamniotes, N-methyl-D-aspartate (NMDA) was also found to excite these afferents. Kynurenic acid reversibly reduced the resting firing rates of the afferents and the increases in firing due to the application of glutamate and aspartate. These findings provide preliminary support for the hypothesis that glutamate (or a related compound) is also a vestibular hair cell transmitter in amniotes.

Action Potentials↗
PubMed1995

Dynamic properties of the human vestibulo-ocular reflex during head rotations in roll.

We investigated the dynamic properties of the human vestibulo-ocular reflex (VOR) during roll head rotations in three human subjects using the magnetic search coil technique. In the first of two experiments, we quantify the behavior of the ocular motor plant in the torsional plane. The subject's eye was mechanically displaced into intorsion, extorsion or abduction, and the dynamic course of return of the eye to its resting position was measured. The mean predominant time constants of return were 210 msec from intorsion, 83 msec from extorsion, and 217 msec from abduction, although there was considerable variability of results from different trials and subjects. In the second experiment, we quantify the efficacy of velocity-to-position integration of the vestibular signal. Position-step stimuli were used to test the torsional or horizontal VOR, being applied with subjects heads erect or supine. After a torsional position-step, the eye drifted back to its resting position, but after a horizontal position-step the eye held its new horizontal position. To interpret these responses we used a simple model of the VOR with parameters of the ocular motor plant set to values determined during Exp 1. The time constant of the velocity-to-position neural integrator was smaller (typically 2 sec) in the torsional plane than in the horizontal plane (> 20 sec). No disconjugacy of torsional eye movements was observed. Thus, the dynamic properties of the VOR in roll differ significantly from those of the VOR in yaw, reflecting different visual demands placed on this reflex in these two planes.

Adult↗
PubMed1989

Blockade of 5-hydroxytryptamine3 receptors prevents cisplatin-induced but not motion- or xylazine-induced emesis in the cat.

5-Hydroxytryptamine3 antagonists have been reported to prevent emesis elicited by cisplatin and radiation. This study investigated the possibility that drugs with this mechanism of action may be useful in preventing emesis elicited by other stimuli. The drugs ICS 205-930 (0.1 and 1.0 mg/kg) and MDL 72222 (0.1 and 1.0 mg/kg) were administered SC to cats before challenging them with either provocative motion or an emetic dose of xylazine. In no instance was a significant reduction in emesis evident. Zacopride was also administered before motion testing (0.01 to 10.0 mg/kg) and found to not have efficacy. To test the possibility that species or route of administration were factors in the negative results, 1.0 mg/kg of ICS 205-930 was administered SC before IV infusion of 7.5 mg/kg of cisplatin. There was a total suppression of emesis for the duration of the six-hour observation periods. This result verifies other work which found 5-hydroxytryptamine3 antagonists to be effective in preventing emesis elicited by cancer chemotherapeutic treatments. However, there is no evidence that they are effective in other syndromes, such as motion sickness and xylazine-induced emesis.

Animals↗
PubMed1989

8-OH-DPAT suppresses vomiting in the cat elicited by motion, cisplatin or xylazine.

Vomiting was suppressed in cats pretreated with 8-OH-DPAT and then challenged with an emetic stimulus; motion, xylazine or cisplatin. The antiemetic effect is likely due to stimulation of postsynaptic serotonin-1A receptors. The most parsimonious explanation is that it acts at a convergent structure, presumably at or near the vomiting center. If so, 8-OH-DPAT may block emesis elicited by virtually any other stimulus. A supplementary experiment revealed that lorazepam suppressed motion sickness at a dose that produced ataxia, but did not suppress xylazine-induced emesis. These results do not support the possibility that the antiemetic effects of 8-OH-DPAT were the result of anxiolytic activity.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

The reducing agent dithiothreitol (DTT) does not abolish the inhibitory nicotinic response recorded from rat dorsolateral septal neurons.

Previous intracellular recordings have demonstrated that dorsolateral septal nucleus (DLSN) neurons express a novel nicotinic receptor which produces a direct membrane hyperpolarization when activated by nicotinic agonists. Activation of the classical excitatory nicotinic receptors has been shown to require a disulfide bond involving the cysteines at positions 192 and 193 of the alpha subunits of the receptor. Reduction of this cystine bond with dithiothreitol (DTT) abolishes agonist activation of excitatory nicotinic receptors. We have now examined whether DTT treatment of the inhibitory nicotinic receptor on DLSN neurons also abolishes the inhibitory nicotinic response. We find that the inhibitory response persists after treatment of the neurons with 1 mM DTT, even if the reduction is followed by alkylation of the receptor with bromoacetylcholine to prevent possible reformation of disulfide bonds. This result suggests that the agonist binding site on the inhibitory nicotinic receptor does not require an intact disulfide bond, similar to the bond on the alpha subunit of the excitatory nicotinic receptor, for agonist activation of the receptor. Some of these results have been previously reported in abstract form.

Acetylcholine↗
PubMed1993

The correlated blanching of synaptic bodies and reduction in afferent firing rates caused by transmitter-depleting agents in the frog semicircular canal.

Synaptic bodies (SBs) associated with rings of synaptic vesicles and well-defined, pre- and post-synaptic membrane structures are indicators of maturity in most hair cell-afferent nerve junctions. The role of the SBs remains elusive despite several experiments showing that they may be involved in storage of neurotransmitter. Our results demonstrate that SBs of the adult posterior semicircular canal (SCC) cristae hair cells become less electron dense following incubation of the SCC with the transmitter-depleting drug tetrabenazine (TBZ). Objective quantification and comparison of the densities of the SBs in untreated and TBZ-treated frog SCC demonstrated that TBZ significantly decreased the electron density of SBs. This reduction in electron density was accompanied by a reduction in firing rates of afferent fibers innervating the posterior SCC. A second transmitter-depleting drug, guanethidine, previously shown to reduce the electron density of hair cell SBs, also reduced the firing rates of afferent fibers innervating the posterior SCC. In contrast, the electron density of dense granules (DG), similar in size and shape to synaptic bodies (SB) in hair cells, did not change after incubation in TBZ, thus indicating that granules and SBs are not similar in regard to their electron density. The role of SBs in synaptic transmission and the transmitter, if any, stored in the SBs remain unknown. Nonetheless, the association of the lessening of electron density with a reduction in afferent firing rate provides impetus for the further investigation of the SB's role in neurotransmission.

Animals↗