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Boyle, Richard D.

Publications and source records attributed to Boyle, Richard D..

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.

Evaluation of Rodent Spaceflight in the NASA Animal Enclosure Module for an Extended Operational Period (up to 35 days)

The National Aeronautics and Space Administration Animal Enclosure Module (AEM) was developed as a self-contained rodent habitat for shuttle flight missions that provides inhabitants with living space, food, water, ventilation, and lighting for shuttle flight missions, and this study reports whether, after minimal hardware modification, the AEM could support an extended term up to 35 days for Sprague-Dawley rats and C57BL/6 female mice for use on the International Space Station. Success was evaluated based on comparison of AEM housed animals to that of vivarium housed and to normal biological ranges through various measures of animal health and well-being, including animal health evaluations, animal growth and body masses, organ masses, rodent food bar consumption, water consumption, and analysis of blood contents. The results of this study confirmed that the AEMs could support 12 adult female C57BL/6 mice for up to 35 days with self-contained RFB and water, and the AEMs could also support 5 adult male Sprague-Dawley rats for 35 days with external replenishment of diet and water. This study has demonstrated the capability and flexibility of the AEM to operate for up to 35 days with minor hardware modification. Therefore, with modifications, it is possible to utilize this hardware on the International Space Station or other operational platforms to extend the space life science research use of mice and rats.

Animal enclosure module

Functional Responses in Otolith Structures from Micro- to Hyper-Gravity

Vertebrates and invertebrates sense gravito-inertial acceleration by mechanoreceptors in the otolith and statolith organs, respectively. These structures consist of ciliated sensory hair cells surmounted by biomineral grains of calcium carbonate (CaCO3) called oto-orstato-conia. The grains provide mechanical loading of hair cell cilia, and their high density increases sensitivity to acceleration. A widely considered mechanism by which the animal responds to a chronic change in amplitude of gravity is a change in weight lending otoconia. In G, it is argued, the organism counters the loss of gravity by increasing CaCO3 production, thereby increasing otolith mass, as a means to increase system gain. In hypergravity (HG), the converse is argued. Here, we present the results obtained in 3 species exposed both to G and HG. Adult toadfish, Opsanus tau, were exposed to G in 2 short-duration shuttle missions and to 1.24 1.73G centrifugation for 1-32 days; re-adaptation was studied following 1-8 days of 1G. Results show a biphasic pattern in response to 1.73G: 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. Next, we examined directly the responses of statocyst receptors in the land snail after exposure to G on two unmanned Russian Orbital missions and at 1.24G. Similar to vertebrate afferents snail receptors increased their sensitivity to tilt after G exposure, and decrease it after 16-32 days of HG. 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. Support Contributed By: NASA 03-OBPR-04 and 11-11_Omni_2-0002

Vertebrates

Exploratory Study for Continuous-time Parameter Estimation of Ankle Dynamics

Recently, a parallel pathway model to describe ankle dynamics was proposed. This model provides a relationship between ankle angle and net ankle torque as the sum of a linear and nonlinear contribution. A technique to identify parameters of this model in discrete-time has been developed. However, these parameters are a nonlinear combination of the continuous-time physiology, making insight into the underlying physiology impossible. The stable and accurate estimation of continuous-time parameters is critical for accurate disease modeling, clinical diagnosis, robotic control strategies, development of optimal exercise protocols for longterm space exploration, sports medicine, etc. This paper explores the development of a system identification technique to estimate the continuous-time parameters of ankle dynamics. The effectiveness of this approach is assessed via simulation of a continuous-time model of ankle dynamics with typical parameters found in clinical studies. The results show that although this technique improves estimates, it does not provide robust estimates of continuous-time parameters of ankle dynamics. Due to this we conclude that alternative modeling strategies and more advanced estimation techniques be considered for future work.

neuromuscular systems

An Indirect System Identification Technique for Stable Estimation of Continuous-Time Parameters of the Vestibulo-Ocular Reflex (VOR)

The vestibulo-ocular reflex (VOR) is a well-known dual mode bifurcating system that consists of slow and fast modes associated with nystagmus and saccade, respectively. Estimation of continuous-time parameters of nystagmus and saccade models are known to be sensitive to estimation methodology, noise and sampling rate. The stable and accurate estimation of these parameters are critical for accurate disease modelling, clinical diagnosis, robotic control strategies, mission planning for space exploration and pilot safety, etc. This paper presents a novel indirect system identification method for the estimation of continuous-time parameters of VOR employing standardised least-squares with dual sampling rates in a sparse structure. This approach permits the stable and simultaneous estimation of both nystagmus and saccade data. The efficacy of this approach is demonstrated via simulation of a continuous-time model of VOR with typical parameters found in clinical studies and in the presence of output additive noise.

Kukreja, Sunil L.

Plasticity of Neurovestibular Systems Following Micro- and Hyper-Gravity Exposure and Readaptation to Earth's 1G

The gravity-sensing organs sense the sum of inertial force due to head translation and head orientation relative to gravity. Normally gravity is constant, and yet the neural sensors show remarkable plasticity. When the force of gravity changes, such as in spaceflight or during centrifugation, the neurovestibular system responds by regulating its neural output, and this response is similar for the vertebrate utricular nerve afferents and for the statocyst hair cell in invertebrates. First, we examine the response of utricular afferents in toadfish following exposure to G on two orbital missions (STS-90 and 95). Within the first day after landing, magnitude of neural response to an applied acceleration was significantly elevated, and re-adaptation back to control values occurred within approximately 30 hours. Time course of return to normal approximately parallels the decrease in vestibular disorientation in astronauts following return. Next, we use well-controlled hyper-G experiments in the vertebrate model to address: If G leads to adaptation and subsequent re-adaptation neural processes, does the transfer from 1G to hyper-G impart the opposite effects and do the effects accompanying transfer from the hyper-G back to the 1G conditions resemble as an analog the transfer from 1G to the microG Results show a biphasic pattern in reaction to 3G exposures: an initial sensitivity up-regulation (3- and 4-day) followed by a significant decrease after longer exposure. Return to control values is on the order of 4-8 days. Utricular sensitivity is strongly regulated up or down by gravity load and the duration of exposure. Interestingly, we found no correlation of response and hair cell synaptic body counts despite the large gain difference between 4- and 16-Day subjects. Lastly, we examine responses of statocyst receptors in land snail following exposure to G on two unmanned Russian Orbital missions (Foton M-2 and -3). Here, we have the ability to measure the output directly from the hair cells. Similar to afferents in vertebrates the hair cells increased their response sensitivity to vestibular stimulation. Two major pieces of information are needed: the precise vertebrate hair cell response to altered gravity and the impact of longer duration exposures on sensory plasticity.

Boyle, Richard D.

A Sparse Matrix Approach for Simultaneous Quantification of Nystagmus and Saccade

The vestibulo-ocular reflex (VOR) consists of two intermingled non-linear subsystems; namely, nystagmus and saccade. Typically, nystagmus is analysed using a single sufficiently long signal or a concatenation of them. Saccade information is not analysed and discarded due to insufficient data length to provide consistent and minimum variance estimates. This paper presents a novel sparse matrix approach to system identification of the VOR. It allows for the simultaneous estimation of both nystagmus and saccade signals. We show via simulation of the VOR that our technique provides consistent and unbiased estimates in the presence of output additive noise.

Kukreja, Sunil L.

The Role of Possible Feedback Mechanisms in the Effects of Altered Gravity on Formation and Function of Gravireceptors of Mollusks and Fish

The variety of the effects of altered gravity (AG) on development and function of gravireceptors cannot be explained by simple feedback mechanism that correlates gravity level and weight of test mass. The reaction of organisms to the change of gravity depends on the phase of their development. To predict this reaction we need to know the details of the mechanisms of gravireceptor formation

Kondrachuk, Alexander V.