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PubMed1986

Dexamethasone mimicks the antimotion sickness effects of amphetamine and scopolamine.

Based on preliminary suggestions that individual differences in susceptibility to stressful motion might be related to physiological differences in responses of the hypothalamic-pituitary-adrenal axis, we tested the efficacy of dexamethasone and metyrapone in subjects exposed to cross-coupled accelerative semicircular canal stimulation on a rotating chair. Subjects given 0.5 mg of dexamethasone every 6 h for 48 h could endure 80% more stressful motion (P = 0.03) in a within-subjects design study, whereas, no improvement followed treatment with 750 mg of metyrapone[correction of metryapone] every 4 h for 24 h. The efficacy of dexamethasone might be explained in terms of its neurochemical actions on several neurotransmitter systems which are also modulated by such classical antimotion sickness drugs as amphetamine and scopolamine. Because dexamethasone induces adaptive changes within the central nervous system it may prove superior to scopolamine and amphetamine which possess significant side effects, are short acting, and rapidly tolerated.

Adrenocorticotropic Hormone↗
PubMed1987

Spacelab experiments on space motion sickness.

Recent research results from ground and flight experiments on motion sickness and space sickness conducted by the Man Vehicle Laboratory are reviewed. New tools developed include a mathematical model for motion sickness, a method for quantitative measurements of skin pallor and blush in ambulatory subjects, and a magnitude estimation technique for ratio scaling of nausea or discomfort. These have been used to experimentally study the time course of skin pallor and subjective symptoms in laboratory motion sickness. In prolonged sickness, subjects become hypersensitive to nauseogenic stimuli. Results of a Spacelab-1 flight experiment are described in which four observers documented the stimulus factors for and the symptoms/signs of space sickness. The clinical character of space sickness differs somewhat from acute laboratory motion sickness. However SL-1 findings support the view that space sickness is fundamentally a motion sickness. Symptoms were subjectively alleviated by head movement restriction, maintenance of a familiar orientation with respect to the visual environment, and wedging between or strapping onto surfaces which provided broad contact cues confirming the absence of body motion.

Adaptation, Physiological↗
PubMed1987

Space motion sickness preflight adaptation training: preliminary studies with prototype trainers.

Preflight training frequently has been proposed as a potential solution to the problem of space motion sickness. The paper considers successively the otolith reinterpretation, the concept for a preflight adaptation trainer and the research with the Miami University Seesaw, the Wright Patterson Air-Force Base Dynamic Environment Simulator and the Visually Coupled Airborne Systems Simulator prototype adaptation trainers.

Adaptation, Physiological↗
PubMed1988

Vestibular factors influencing the biomedical support of humans in space.

This paper will describe the biomedical support aspects of humans in space with respect to the vestibular system. The vestibular system is thought to be the primary sensory system involved in the short-term effects of space motion sickness although there is increasing evidence that many factors play a role in this complex set of symptoms. There is the possibility that an individual's inner sense of orientation may be strongly coupled with the susceptibility to space motion sickness. A variety of suggested countermeasures for space motion sickness will be described. Although there are no known ground-based tests that can predict space motion sickness, the search should go on. The long term effects of the vestibular system in weightlessness are still relatively unknown. Some preliminary data has shown that the otoconia are irregular in size and distribution following extended periods of weightlessness. The ramifications of this data are not yet known and because the data was obtained on lower order animals, definitive studies and results must wait until the space station era when higher primates can be studied for long durations. This leads us to artificial gravity, the last topic of this paper. The vestibular system is intimately tied to this question since it has been shown on Earth that exposure to a slow rotating room causes motion sickness for some period of time before adaptation occurs. If the artificial gravity is intermittent, will this mean that people will get sick every time they experience it? The data from many astronauts returning to Earth indicates that a variety of sensory illusions are present, especially immediately upon return to a 1-g environment. Oscillopsia or apparent motion of the visual surround upon head motion along with inappropriate eye motions for a given head motion, all indicate that there is much to be studied yet about the vestibular and CNS systems reaction to a sudden application of a steady state acceleration field like 1-g. From the above information it is obvious that the vestibular system does have unique requirements when it comes to the biomedical support of space flight. This is not to say that other areas such as cardiovascular, musculo-skeletal, immunological and hematological systems do not have their own unique requirements but that possible solutions to one system can provide continuing problems to another system. For example, artificial gravity might be helpful for long term stabilization of bone demineralization or cardiovascular deconditioning but might introduce a new set of problems in orientation, vestibular conflict and just plain body motion in a rotating space vehicle.

Acceleration↗
PubMed1992

Tonic vibration reflexes and background force level.

On Earth, the functional stretch reflex is an important component in the maintenance of posture and muscle tone. In parabolic flight experiments, we evaluated whether the functional stretch reflex, as reflected in the tonic vibration reflex, adjusts appropriately for changes in background gravitoinertial force level. Virtually immediate alterations of appropriate sign occurred.

Forearm↗
PubMed1992

Ocular torsion as a test of the asymmetry hypothesis of space motion sickness.

Disconjugate eye torsion induced by 0 G and 1.8 G during parabolic flight was studied in nine former astronauts in 1990 and eight in 1991, four of whom were included in the previous experiment. The astronauts could be divided into two statistically significant groups on the basis of low and high scores of disconjugacy. When their histories of space motion sickness (SMS) were later revealed, all of the low scorers had not been sick on previous space flights; all the high scorers had had SMS. These data give support to the hypothesis that SMS in one-half or two-thirds of astronauts is due to an otolith, probably utricular, asymmetry in those persons.

Eye Diseases↗
PubMed1992

Uvula-nodulus and gravity direction (a study on vertical optokinetic-oculomotor functions).

Some characteristics of vertical optokinetic nystagmus and after-nystagmus, in particular, its up/down gain asymmetry, are known to be influenced by gravity direction, which is basically perceived by otolith organs. However, how such an information of gravity direction is processed within the central nervous system is not well understood, even though the role of cerebellar uvula and nodulus in vertical eye movements has been identified for some time. Accordingly, in this study, vertical optokinetic nystagmus and after-nystagmus were studied in squirrel monkeys both in the upright and side-lateral positions (different gravity direction to the head), before and after uvulonodulectomy. When the optokinetic stimulus was given, the slow phase eye velocity of optokinetic nystagmus was significantly higher in the side-lateral position than that obtained in the upright position. This difference disappeared after uvulonodulectomy. When the initial slow phase eye velocity of optokinetic after-nystagmus was compared, the one obtained in the side-lateral position was significantly higher than that acquired in the upright position. This difference also disappeared after the uvulonodular ablation. Thus, in this study of vertical optokinetic nystagmus and after-nystagmus, the role of uvula and nodulus in relaying the information of gravity direction was confirmed.

Animals↗
PubMed1994

Torsional vestibulo-ocular reflex measurements for identifying otolith asymmetries possibly related to space motion sickness susceptibility.

Recent studies by Diamond and Markham have identified significant correlations between space motion sickness susceptibility and measures of disconjugate torsional eye movements recorded during parabolic flights. These results support an earlier proposal by von Baumgarten and Thumler which hypothesized that an asymmetry of otolith function between the two ears is the cause of space motion sickness. It may be possible to devise experiments that can be performed in the 1 g environment on earth that could identify and quantify the presence of asymmetric otolith function. This paper summarizes the known physiological and anatomical properties of the otolith organs and the properties of the torsional vestibulo-ocular reflex which are relevant to the design of a stimulus to identify otolith asymmetries. A specific stimulus which takes advantage of these properties is proposed.

Acceleration↗
PubMed1994

Formation of otoconia in the Japanese red-bellied newt, Cynops pyrrhogaster.

Pre-mated adult female newts and fertilized eggs will be flown on the International Microgravity Laboratory-2 flight, in 1994. One objective of the flight will be to observe the influence of microgravity on the development of the gravity-sensing organs in the inner ear. These organs contain sensory hair cells covered by a layer of dense stones (otoconia). Gravity and linear acceleration exert forces on these masses, leading to excitation of the nerve fibers innervating the hair cells. If the production of the otoliths is regulated to reach an optimal weight, their development might be abnormal in microgravity. Ground-based control experiments are reported describing the developmental sequence in which both the otoliths and their associated sensory epithelium and the semicircular canals appear and develop. Three-dimensional reconstruction of serial sections through the otic vesicle of newt embryos at stages 31 through 58 demonstrate the first appearance, relative position and growth of the otoliths. Reports of experiments in which fertilized frog eggs were flown on a Russian Cosmos mission conclude that the utricular otolith is increased in volume, whereas the saccular otolith maintains normal size, suggesting that at least in the utricle, the weight of the otolith might be regulated.

Acceleration↗
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↗
PubMed1987

Thermal dependence of neural activity in the hamster hippocampal slice preparation.

1. Neural activity was recorded in an in vitro hamster hippocampal slice preparation while the temperature of the Ringer's solution bathing in the slice was controlled at selected levels. 2. The amplitude of the population spike (action potentials from a group of pyramidal cells) was measured as bath temperature was lowered from 35 degrees C to temperatures where a response could not be evoked. 3. Plots of population spike amplitude versus temperature have bell-shaped curves. The population spikes increased in amplitude as temperature was lowered from 35 degrees C, reached a peak amplitude between 25 and 20 degrees C, and then decreased until a response could not be evoked when temperature was further lowered. 4. These in vitro results obtained in the slice preparation are related to in vivo hippocampal studies. Results are interpreted as consistent with the proposal reviewed here that neural activity in the hippocampus plays a role at specific stages of entrance into and arousal from hibernation.

Acclimatization↗
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↗
PubMed1993

Utricular otoconia of some amphibians have calcitic morphology.

This report concerns the morphological features of otoconia removed from the inner ear of four amphibian species. Results from scanning electron microscopic examination are compared based on the site of origin. These results show that utricular otoconia have a mineral structure that mimics calcite, rather than the widely accepted idea that they are mineralized by calcium carbonate of the aragonite polymorph.

Ambystoma mexicanum↗
PubMed1995

Visualization of newt aragonitic otoconial matrices using transmission electron microscopy.

Otoconia are calcified protein matrices within the gravity-sensing organs of the vertebrate vestibular system. These protein matrices are thought to originate from the supporting or hair cells in the macula during development. Previous studies of mammalian calcitic, barrel-shaped otoconia revealed an organized protein matrix consisting of a thin peripheral layer, a well-defined organic core and a flocculent matrix inbetween. No studies have reported the microscopic organization of the aragonitic otoconial matrix, despite its protein characterization. Pote et al. (1993b) used densitometric methods and inferred that prismatic (aragonitic) otoconia have a peripheral protein distribution, compared to that described for the barrel-shaped, calcitic otoconia of birds, mammals, and the amphibian utricle. By using tannic acid as a negative stain, we observed three kinds of organic matrices in preparations of fixed, decalcified saccular otoconia from the adult newt: (1) fusiform shapes with a homogenous electron-dense matrix; (2) singular and multiple strands of matrix; and (3) more significantly, prismatic shapes outlined by a peripheral organic matrix. These prismatic shapes remain following removal of the gelatinous matrix, revealing an internal array of organic matter. We conclude that prismatic otoconia have a largely peripheral otoconial matrix, as inferred by densitometry.

Animals↗
PubMed1996

Cell proliferation and hair cell addition in the ear of the goldfish, Carassius auratus.

Cell proliferation and hair cell addition have not been studied in the ears of otophysan fish, a group of species who have specialized hearing capabilities. In this study we used the mitotic S-phase marker bromodeoxyuridine (BrdU) to identify proliferating cells in the ear of one otophysan species, Carassius auratus (the goldfish). Animals were sacrificed at 3 h or 5 days postinjection with BrdU and processed for immunocytochemistry. The results of the study show that cell proliferation occurs in all of the otic endorgans and results in the addition of new hair cells. BrdU-labeled cells were distributed throughout all epithelia, including the primary auditory endorgan (saccule), where hair cell phenotypes vary considerably along the rostrocaudal axis. This study lays the groundwork for our transmission electron microscopy study of proliferative cells in the goldfish ear (Presson et al., Hearing Research 100 (1996) 10-20) as well as future studies of hair cell development in this species. The ability to predict, based on epithelial location, the future phenotype of developing hair cells in the saccule of the goldfish make that endorgan a particularly powerful model system for the investigation of early hair cell differentiation.

Animals↗
PubMed1990

Vestibular receptor cells and signal detection: bioaccelerometers and the hexagonal sampling of two-dimensional signals.

The inner ear contains sensory organs which signal changes in head movement. The vestibular sacs, in particular, are sensitive to linear accelerations. Electron microscopic images have revealed the structure of tiny sensory hair bundles, whose mechanical deformation results in the initiation of neuronal activity and the transmission of electrical signals to the brain. The structure of the hair bundles is shown in this paper to be that of the most efficient two-dimensional phased-array signal processors.

Acceleration↗
PubMed1990

Toward modeling a dynamic biological neural network.

Mammalian macular endorgans are linear bioaccelerometers located in the vestibular membranous labyrinth of the inner ear. In this paper, the organization of the endorgan is interpreted on physical and engineering principles. This is a necessary prerequisite to mathematical and symbolic modeling of information processing by the macular neural network. Mathematical notations that describe the functioning system were used to produce a novel, symbolic model. The model is six-tiered and is constructed to mimic the neural system. Initial simulations show that the network functions best when some of the detecting elements (type I hair cells) are excitatory and others (type II hair cells) are weakly inhibitory. The simulations also illustrate the importance of disinhibition of receptors located in the third tier in shaping nerve discharge patterns at the sixth tier in the model system.

Acceleration↗
PubMed1996

A mechanism of adaptation to hypergravity in the statocyst of Aplysia californica.

The gravity-sensing organ of Aplysia californica consists of bilaterally paired statocysts containing statoconia, which are granules composed of calcium carbonate crystals in an organic matrix. In early embryonic development, Aplysia contain a single granule called a statolith, and as the animal matures, statoconia production takes place. The objective of this study was to determine the effect of hypergravity on statoconia production and homeostasis and explore a possible physiologic mechanism for regulating this process. Embryonic Aplysia were exposed to normogravity or 3 x g or 5.7 x g and each day samples were analyzed for changes in statocyst, statolith, and body dimensions until they hatched. In addition, early metamorphosed Aplysia (developmental stages 7-10) were exposed to hypergravity (2 x g) for 3 weeks, and statoconia number and statocyst and statoconia volumes were determined. We also determined the effects of hypergravity on statoconia production and homeostasis in statocysts isolated from developmental stage 10 Aplysia. Since prior studies demonstrated that urease was important in the regulation of statocyst pH and statoconia formation, we also evaluated the effect of hypergravity on urease activity. The results show that hypergravity decreased statolith and body diameter in embryonic Aplysia in a magnitude-dependent fashion. In early metamorphosed Aplysia, hypergravity decreased statoconia number and volume. Similarly, there was an inhibition of statoconia production and a decrease in statoconia volume in isolated statocysts exposed to hypergravity in culture. Urease activity in statocysts decreased after exposure to hypergravity and was correlated with the decrease in statoconia production observed. In short, there was a decrease in statoconia production with exposure to hypergravity both in vivo and in vitro and a decrease in urease activity. It is concluded that exposure to hypergravity downregulates urease activity, resulting in a significant decrease in the formation of statoconia.

Analysis of Variance↗