Ontogeny of Mouse Vestibulo-Ocular Reflex Following Genetic or Environmental Alteration of Gravity Sensing

Abstract

The vestibular organs consist of complementary sensors: the semicircular canals detect rotations while the otoliths detect linear accelerations, including the constant pull of gravity. Several fundamental questions remain on how the vestibular system would develop and/or adapt to prolonged changes in gravity such as during long-term space journey. How do vestibular reflexes develop if the appropriate assembly of otoliths and semi-circular canals is perturbed? The aim of present work was to evaluate the role of gravity sensing during ontogeny of the vestibular system. In otoconia-deficient mice (ied), gravity cannot be sensed and therefore maculo-ocular reflexes (MOR) were absent. While canals-related reflexes were present, the ied deficit also led to the abnormal spatial tuning of the horizontal angular canal-related VOR. To identify putative otolith-related critical periods, normal C57Bl/6J mice were subjected to 2G hypergravity by chronic centrifugation during different periods of development or adulthood (Adult-HG) and compared to non-centrifuged (control) C57Bl/6J mice. Mice exposed to hypergravity during development had completely normal vestibulo-ocular reflexes 6 months after end of centrifugation. Adult-HG mice all displayed major abnormalities in maculo-ocular reflexe one month after return to normal gravity. During the next 5 months, adaptation to normal gravity occurred in half of the individuals. In summary, genetic suppression of gravity sensing indicated that otolith-related signals might be necessary to ensure proper functioning of canal-related vestibular reflexes. On the other hand, exposure to hypergravity during development was not sufficient to modify durably motor behaviour. Hence, 2G centrifugation during development revealed no otolith-specific critical period.

Changes in C57BL6 Mouse Hippocampal Transcriptome Induced by Hypergravity Mimic Acute Corticosterone-Induced Stress

“…We confirmed that (1) C57BL6 mice exposed for 21 days to hypergravity showed an increase of their corticosterone plasma levels, (2) the previously reported variability of the individual adaptation to gravity modifications was indeed present (Beraneck et al, 2012; Gnyubkin et al, 2015). …”

Dynamic characteristics of otolith ocular response during counter rotation about dual yaw axes in mice

“…There are several experiments about mouse OVAR, but mostly, they focused on the estimation of peripheral otolith function, one aspect of this paradigm, at a single tilt angle (Harrod and Baker, 2003; Beraneck et al, 2012; Romand et al, 2013). On the other hand, Killian and Baker (2002) specifically investigated a higher vestibular system by observing bias components at 90 deg of tilt.…”

“…Significant difference in torsion, which was greater on the centrifuge than on the static tilted-chair, suggested that the dorso-ventral shear force was important for generating a larger ocular torsion, otherwise, it could be due to the larger gravity vector acting on the otolith organs and body tilt receptors (Miller and Graybiel, 1971; Yates et al, 2000). In the past, a study of the mouse OVAR at a single tilt angle of 17 deg reported that the vertical eye position modulated ± 8.5 deg for the rotation velocity of 50 deg/s (Beraneck et al, 2012). Compared with this value, our data showed a slightly larger value (± 10.9 deg) at 72 deg/s about equivalent tilt of 20 deg.…”

“…In human subjects, these eye movements during OVAR are likely associated with motion sickness showing a clear correlation between bias components and its sensitivity (Ventre-Dominey et al, 2008; Dai et al, 2011). Although there are several studies of mouse OVAR, so far only data from the limited range of stimulus are available (Killian and Baker, 2002; Harrod and Baker, 2003; Beraneck et al, 2012; Romand et al, 2013). In this study, we used a counter rotation centrifuge to generate a dynamic rotational force (pseudo-OVAR) greater than that which can be generated by conventional OVAR stimulation at any tilt angle or velocity (Kaufman et al, 2002, 2005).…”

Development of Vestibular Systems in Altered Gravity

“…However, these experiments are open to all types of parameter variations, including the duration of hypergravity period, its strength, etc. Another way of testing for g-related critical periods in vestibular development might be to use otolith-deficient strains of animals, including mice (Harrod and Baker, 2003;Beraneck et al, 2012) or fish (Riley and Moorman, 2000;Ijiri et al, 2003). However, genetically modified strains will only help to support the first of the three requirements, i.e., the demonstration of a general susceptibility of the organism to a modified gravity input, or could help to find basic answers about the sites of adaptation to altered gravity.…”