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At least 397 records · Page 22

The Use of Altered Gravity as a Tool to Understand Neurovestibular Mechanisms in Vertebrates

Vertebrates sense gravito-inertial acceleration by mechanoreceptors (hair cells) in the otolith structures of the inner ear. These structures consist of ciliated sensory hair cells surmounted by biomineral grains of calcium carbonate (CaCO3) called otoconia that provide mechanical loading of hair cell cilia. Changes in their high density can alter the hair cells sensitivity to acceleration and orientation with respect to gravity. A widely considered mechanism by which the animal responds to a chronic change in amplitude of gravity is a change in weight-lending otoconia. Hair cells are synaptically coupled to the vestibular nerve afferents that convey the signals into the brain. Synapses are modifiable in strength and numbers, and thereby can be an additional target to adjust the sensation as the gravity load changes. Here, we present the results obtained in 2 species exposed both to G and HG. Adult toadfish, Opsanus tau, were exposed to G in 2 short-duration shuttle missions and to 1.4 2.24G [resultant] centrifugation for 1-32 days; re-adaptation was studied following 1-8 days after return to 1G. Results show a biphasic pattern in response to 2.24G: initial hypersensitivity, similar to that observed after G exposure, followed by transition to a significant decrease at 16-32 days. Recovery from HG exposure is 4-8 days. Two major pieces of information are still needed: vertebrate hair cell response to altered gravity and impact of longer duration exposures on sensory plasticity. To address the latter we applied electron microscopic techniques to image otoconia mass obtained from 1) mice subjected to 91-days of weightlessness in the Mouse Drawer System (MDS) flown on International Space Station, 2) mice subjected to 91-days of 1.24G centrifugation on ground, and 3) mice flown on 2 short-duration orbital missions. Images indicate a clear restructuring of individual otoconia, suggesting deposition to the outer shell. Images from their HG counterparts indicate the converse - an ablation of the otoconia mass. For shorter duration exposures to weightlessness on 13-day shuttle missions mice otoconia appear normal. Despite the permanence of 1G in evolution the animal senses exposure to a novel, non-1G, environment and adaptive mechanisms are initiated - in the short term compensation is likely confined to the peripheral sensory receptors, the brain or both. For longer exposures structural modifications of the endorgan may also result.

vertebrate↗

Vestibulo-Spinal Pathways in Tetrapods: Chapter - 6.26

The vestibulospinal system provides the spinal motor circuits controlling head/neck and limb movements and body posture with rapid reflex adjustments to maintain equilibrium and stability and with a continuous essential excitatory drive, called tonus, to enhance reactive responses to perturbations that force the animal off normal posture. The sensory signals to these reflex circuits originate from hair cells in the inner ear of otolith structures, namely the utricle and saccule, that transduce inertial acceleration and orientation of the head with respect to gravity and in the three orthogonally arranged semicircular canals that transduce angular head rotation. The principal vestibulospinal pathways are 1) the medial vestibulospinal tract that descends in the ventromedial funiculus and innervates inter- and motoneurons located mainly in lamina VII, VIII, and dorsomedial IX throughout the cervical segments; and 2) the lateral vestibulospinal tracts that course in the lateral to ventrolateral funiculi and are distinguished by two divisions: i) a cervical-projecting tract that overlaps many of the targets of medial vestibulospinal tract neurons including the motoneurons in ventromedial IX and also contributes to reflex control of shoulder and forelimb (arm) muscles; and ii) a lumbosacral-projecting tract that provides a rapid input to maintain stable posture and reflex control of the lower body. A striking observation in understanding the functional organization of this sensory-motor system is both that the driving sensory input can be dynamically modified by the behavioral context in which the sensation is made and that it remains able to quickly respond to an external force during self-generated head movements. The structural basis for vestibulospinal inputs to spinal motor control circuits in quadrupeds and bipeds rely in part on the animal's need for coordination between fore- and hind-limb reflex movements. Understanding the sensory-to-motor transformations in the diverse species rely on the correlations of the conserved and unique species behavior, morphology and physiologic function.

Spinal Cord↗

Neural Mechanisms to the Space Environment

Highly conserved neural systems have evolved to sense the inertial forces due to head translation and head tilt relative to gravitational vertical. These structures consist of ciliated mechanosensitive receptor cells inserted into a neuroepithelium surmounted by biomineral grains of calcium carbonate (CaCO3) called oto- (vertebrates) or stato-conia (invertebrates). Detection of these forces by receptor cells relies on the CaCO3 mass being weighted in Earths 1G. A change in gravity or orientation with respect to gravity has a profound effect on how an organism interacts with its environment, and it is evident that the nervous system responds to the new gravity state. This response might involve the peripheral receptors, the CaCO3 mass, the brain or any combination of these mechanisms based on the intensity and duration of the gravity change. Here, we examine the arguments supporting the different mechanisms of adaptation to the space environment. First, a pre- or post-synaptic alteration in the strength of synaptic transmission between the receptor cell and nerve afferent can adjust the system output. The number of synaptic ribbons in certain type II hair cells in rodent is labile, increasing following exposure to microgravity. An increase in number of synaptic ribbons in toadfish otolith hair cells following exposure to microgravity could potentially explain the observed afferent hypersensitivity to acceleration postflight. The physiological findings in the isolated statocyst in snails are in line with the vertebrate data, and conform to the proposition that G exposure leads to changes in gravireceptor function. At the same time this similarity in neural response to G exposure between the vertebrates and invertebrates is intriguing: the increased neural sensitivity in the vertebrate was detected in the nerve afferents, one synapse away from the receptor cell, whereas the increased neural sensitivity observed in the snail was detected directly at the receptor level. Second, the CaCO3 mass provides mechanical loading of receptor cell cilia, and their density alters sensitivity. A widely considered mechanism by which the animal responds to a chronic change in amplitude of gravity is a change in weight-lending CaCO3 mass. In G, it is argued, the organism counters the loss of gravity by increasing CaCO3 production, thereby increasing its mass, as a means to increase system gain. In hypergravity, the converse is argued. Earlier evidence in mollusks and recent results in mice suggest a remodeling might occur, especially after long-term space exposure. Lastly, we have to distinguish at least two kinds of neural feedbacks. One is connected with local mechanisms of self-regulation and specific for initial period of organ development when the neural connections are still absent. And the other feedback is related to neural self-regulation and specific for later stages of the organ development, and includes an efferent vestibular feedback. Complexity of the problem is enhanced by incompleteness of experiments, and consequently the experimental results have not led to a clear interpretation despite the numerous studies.

Boyle, Richard D.↗

Neuro-vestibular Examination During and Following Spaceflight

Adaptation to microgravity during spaceflight causes neurological disturbances that are either directly or indirectly mediated by the vestibular system. These disturbances could include space motion sickness, spatial disorientation, cognitive impairment, as well as changes in head-eye coordination, vestibulo-ocular reflex, and strategies for controlling posture and locomotion. It seems that otolith-mediated reflex gain adapts rapidly over time during spaceflight and after landing. However, animal studies have shown that structural modifications of the vestibular sensory apparatus develop during long-duration spaceflight. To date, no studies have characterized the severity of vestibular syndromes experienced by astronauts as a function of the duration of spaceflight, or whether the effects are caused by changes at the peripheral end organs, midbrain, cerebellum, or vestibular cortex.

Clément, G.↗

Results of Life Sciences DSOs Conducted aboard the Space Shuttle: 1988-1990

Results are presented for a collection of life sciences investigations sponsored by the Space Biomedical Research Institute and Biomedical Research Operations at the NASA Lyndon B. Johnson Space Center and conducted as Detailed Supplementary Objectives (DSOs) on Space Shuttle flights between 1988 and 1990. Reports were grouped into grouped into four primary sections: Orthostatic Function, Neurophysiology, Biomedical Physiology, and Radiation Monitoring. The DSOs included in this report are: - DSO 460: Changes in Total Body Water During Space Flight - DSO 466: Pre- and Postflight Cardiovascular Assessment/Interim Report - DSO 467: Influence of Weightlessness of Baroreflex Function - DSO 459: Otolith Tilt-Translation Reinterpretation - DSO 450: Salivary Cortisol Levels During the Acute Phases of Space Flight - DSO 458: In-flight Pharmacokinetics of Acetaminophen in Saliva - DSO 469A: Low Earth Orbit Radiation Dose Distribution in a Phantom Head - DSO 469B: Active Dosimetric Measurements on Shuttle Flights/Interim Report - DSO 469C: Neutron Spectrum and Dose-Equivalent in Shuttle Flights During Solar Maximum

Carolyn S Leach↗

The relation of motion sickness to the spatial-temporal properties of velocity storage

Tilting the head in roll to or from the upright while rotating at a constant velocity (roll while rotating, RWR) alters the position of the semicircular canals relative to the axis of rotation. This produces vertical and horizontal nystagmus, disorientation, vertigo, and nausea. With recurrent exposure, subjects habituate and can make more head movements before experiencing overpowering motion sickness. We questioned whether promethazine lessened the vertigo or delayed the habituation, whether habituation of the vertigo was related to the central vestibular time constant, i.e., to the time constant of velocity storage, and whether the severity of the motion sickness was related to deviation of the axis of eye velocity from gravity. Sixteen subjects received promethazine and placebo in a double-blind, crossover study in two consecutive 4-day test series 1 month apart, termed series I and II. Horizontal and vertical eye movements were recorded with video-oculography while subjects performed roll head movements of approx. 45 degrees over 2 s to and from the upright position while being rotated at 138 degrees /s around a vertical axis. Motion sickness was scaled from 1 (no sickness) to an endpoint of 20, at which time the subject was too sick to continue or was about to vomit. Habituation was determined by the number of head movements that subjects made before reaching the maximum motion sickness score of 20. Head movements increased steadily in each session with repeated testing, and there was no difference between the number of head movements made by the promethazine and placebo groups. Horizontal and vertical angular vestibulo-ocular reflex (aVOR) time constants declined in each test, with the declines being closely correlated to the increase in the number of head movements. The strength of vertiginous sensation was associated with the amount of deviation of the axis of eye velocity from gravity; the larger the deviation of the eye velocity axis from gravity, the more severe the motion sickness. Thus, promethazine neither reduced the nausea associated with RWR, nor retarded or hastened habituation. The inverse relationship between the aVOR time constants and number of head movements to motion sickness, and the association of the severity of motion sickness with the extent, strength, and time of deviation of eye velocity from gravity supports the postulate that the spatiotemporal properties of velocity storage, which are processed between the nodulus and uvula of the vestibulocerebellum and the vestibular nuclei, are likely to represent the source of the conflict responsible for producing motion sickness.

NASA Discipline Neuroscience↗

Model of statoconia accumulation in gravireceptors of mollusks

The kinetics of formation and accumulation of statoconia are different for Aplysia californica and Biomphalaria glabrata. In Aplysia californica, the fast growth of statoconia number occurs after the critical size (approximately 45 micrometers) of statocyst is reached; then the increase of statoconia number is proceeding with the nonmonotonic rate during the life of an animal. In Biomphalaria the growth of statoconia number occurs only in the initial phase. Then long-term evolution of statoconia in the absence of their generation is the result of their growth in the cyst lumen. In the case of Aplysia californica it is not clear whether a temporal change of the statoconia size distribution (SSD) is caused by statoconia growth in the cyst lumen similar to that in Biomphalaria (Model 1) or statoconia growth takes place in supporting cells until their release into the cyst lumen occurs. (Model 2). This problem is of practical importance because the majority of experiments related to the development of molluscan gravireceptors in altered gravity dealt with an initial phase of statoconia evolution in Aplysia californica and Biomphalaria glabrata. The purpose of the present work is the application of mathematical modeling to the analysis of mechanisms of statoconia formation by supporting cells.

Non-NASA Center↗

Effects of microgravity on vestibular ontogeny: direct physiological and anatomical measurements following space flight (STS-29)

Does space flight change gravity receptor development? The present study measured vestibular form and function in birds flown as embryos for 5 days in earth orbit (STS-29). No major changes in vestibular gross morphology were found. Vestibular response mean amplitudes and latencies were unaffected by space flight. However, the results of measuring vestibular thresholds were mixed and abnormal responses in 3 of the 8 flight animals raise important questions.

NASA Discipline Neuroscience↗

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.

NASA Program Space Physiology and Countermeasures↗

Introduction: an overview of gravity sensing, perception, and signal transduction in animals and plants

The antiquity of biological sensitivity and response to gravity can be traced through the ubiquity of morphology, mechanisms, and cellular events in gravity sensing biological systems in the most diverse species of both plants and animals. Further, when we examine organisms at the cellular level to elucidate the molecular mechanism by which a gravitational signal is transduced into a biochemical response, the distinction between plants and animals becomes blurred.

NASA Center HQS↗

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.

Non-NASA Center↗

Production of otoconia in the endolymphatic sac in the Japanese red-bellied newt, Cynops pyrrhogaster: light and transmission electron microscopic study

The formation of otoconia in the endolymphatic sac (ES) of the larval newt, Cynops pyrrhogaster, has been studied by light and transmission electron microscopy. Some of the epithelial cells of the ES contain an abundance of swollen vesicles, Golgi complexes, rough endoplasmic reticula and ribosomes at the late larval stages 50 and 51, approximately 26-30 days after eggs are laid. Five days later, at stage 52, crystals are present in the vacuoles between the epithelial cells. Serial sections indicate that these vacuoles actually form small canals which lie in the wall and join the lumen of the ES. Reconstruction of the ES shows that several canals are contained in the ES wall. At stage 56, about 72 days after eggs are laid, a large number of otoconia are present in the ES lumen, while the otoconia disappear from the canals. It appears that the otoconia are first produced in the canals and then released to the lumen. Some epithelial cells of the ES are thought to expel the organic and inorganic material to the canals to form the otoconia in situ. The process of formation of the otoconia in the ES is discussed.

Non-NASA Center↗

Development of the endolymphatic sac and duct in the Japanese red-bellied newt, Cynops pyrrhogaster

The development and maturation of the endolymphatic sac (ES) and duct (ED) were studied in the newt Cynops pyrrhogaster. The ES first appears as an oval capsule at the dorsal-medial tip of the otic vesicle at stage 39, about 11 days after oviposition. The ES consists of polymorphous epithelial cells with a minimum of cytoplasm. The intercellular space (IS) between the epithelial cells is narrow and has a smooth surface. At stage 44, the size of the ES increases as many vacuoles in the IS become filled. At stage 46, 18 days after oviposition, the ES elongates markedly and a slit-like lumen is found in the ES. The epithelium contains a few cell organelles which are scattered in the cytoplasm. The vacuoles in the IS are fused, which expands the IS. Two days later (stage 48), floccular material (endolymph) is present in the expanded lumen. The IS dilates and has a wide and irregular appearance. At stage 50, approximately 26 days after oviposition, the ES extends and expands significantly and crystals (otoconia) can now be seen in the widened lumen of the ES. The cytoplasm of the cuboidal epithelial cells contains an abundance of vesicles surrounded by ribosomes and Golgi complexes. Intercellular digitations are formed in the expanded IS. At stage 54, the ES forms a large bellow-like pouch. Numerous otoconia accumulate in the lumen. Free floating cells and cell debris can be seen in the lumen at this stage. The epithelial cells contain numerous cytoplasmic organelles which are evenly distributed in the cytoplasm. Granules are found in the apical and lateral cytoplasm. The IS is loose and displays a labyrinthine appearance. The primitive ED first appears as a connection between the ES and the saccule but no lumen is present inside at stage 39. At stage 46, a narrow lumen is formed in the ED, which corresponds to the formation of the ES lumen. At stage 50, as the ED extends, floccular material is seen in the lumen. At stage 54, the ED bears numerous microvilli on its luminal surface. Otoconia and endolymph are present in the ED. Tight junctions between the epithelial cells are formed at stage 46. A fully developed intercellular junctional complex is produced at stage 54. Based on the development of the ES and ED, the maturation of function of the ES and ED are discussed.

NASA Discipline Neuroscience↗

Altered astronaut lower limb and mass center kinematics in downward jumping following space flight

Astronauts exposed to the microgravity conditions encountered during space flight exhibit postural and gait instabilities upon return to earth that could impair critical postflight performance. The aim of the present study was to determine the effects of microgravity exposure on astronauts' performance of two-footed jump landings. Nine astronauts from several Space Shuttle missions were tested both preflight and postflight with a series of voluntary, two-footed downward hops from a 30-cm-high step. A video-based, three-dimensional motion-analysis system permitted calculation of body segment positions and joint angular displacements. Phase-plane plots of knee, hip, and ankle angular velocities compared with the corresponding joint angles were used to describe the lower limb kinematics during jump landings. The position of the whole-body center of mass (COM) was also estimated in the sagittal plane using an eight-segment body model. Four of nine subjects exhibited expanded phase-plane portraits postflight, with significant increases in peak joint flexion angles and flexion rates following space flight. In contrast, two subjects showed significant contractions of their phase-plane portraits postflight and three subjects showed insignificant overall changes after space flight. Analysis of the vertical COM motion generally supported the joint angle results. Subjects with expanded joint angle phase-plane portraits postflight exhibited larger downward deviations of the COM and longer times from impact to peak deflection, as well as lower upward recovery velocities. Subjects with postflight joint angle phase-plane contraction demonstrated opposite effects in the COM motion. The joint kinematics results indicated the existence of two contrasting response modes due to microgravity exposure. Most subjects exhibited "compliant" impact absorption postflight, consistent with decreased limb stiffness and damping, and a reduction in the bandwidth of the postural control system. Fewer subjects showed "stiff" behavior after space flight, where contractions in the phase-plane portraits pointed to an increase in control bandwidth. The changes appeared to result from adaptive modifications in the control of lower limb impedance. A simple 2nd-order model of the vertical COM motion indicated that changes in the effective vertical stiffness of the legs can predict key features of the postflight performance. Compliant responses may reflect inflight adaptation due to altered demands on the postural control system in microgravity, while stiff behavior may result from overcompensation postflight for the presumed reduction in limb stiffness inflight.

Clinical Trial↗

Saccule contribution to immediate early gene induction in the gerbil brainstem with posterior canal galvanic or hypergravity stimulation

Immunolabeling patterns of the immediate early gene-related protein Fos in the gerbil brainstem were studied following stimulation of the sacculus by both hypergravity and galvanic stimulation. Head-restrained, alert animals were exposed to a prolonged (1 h) inertial vector of 2 G (19.6 m/s2) head acceleration directed in a dorso-ventral head axis to maximally stimulate the sacculus. Fos-defined immunoreactivity was quantified, and the results compared to a control group. The hypergravity stimulus produced Fos immunolabeling in the dorsomedial cell column (dmcc) of the inferior olive independently of other subnuclei. Similar dmcc labeling was induced by a 30 min galvanic stimulus of up to -100 microA applied through a stimulating electrode placed unilaterally on the bony labyrinth overlying the posterior canal (PC). The pattern of vestibular afferent firing activity induced by this galvanic stimulus was quantified in anesthetized gerbils by simultaneously recording from Scarpa's ganglion. Only saccular and PC afferent neurons exhibited increases in average firing rates of 200-300%, suggesting a pattern of current spread involving only PC and saccular afferent neurons at this level of stimulation. These results suggest that alteration in saccular afferent firing rates are sufficient to induce Fos-defined genomic activation of the dmcc, and lend further evidence to the existence of a functional vestibulo-olivary-cerebellar pathway of adaptation to novel gravito-inertial environments.

NASA Discipline Neuroscience↗

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.

NASA Program Space Biology↗