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.
Highlights
The vestibular organs consist of complementary sensors: the semicircular canals detect angular accelerations while the otoliths detect linear accelerations, including the constant pull of gravity
AVOR consisted in control mice in horizontal eye movements and little vertical eye movements (Fig. 1A)
Does exposure to hypergravity during development induce long term alteration of maculo-ocular reflexes (MOR) as observed in the adults after fifty days of hypergravity? One month after end of the centrifugation, we found no statistical differences in the Off-vertical axis rotation (OVAR) responses of the Pre and the Post groups compared to controls
Summary
The vestibular organs consist of complementary sensors: the semicircular canals detect angular accelerations while the otoliths detect linear accelerations, including the constant pull of gravity. Most of the central vestibular neurons receive convergent monosynaptic inputs from a single semicircular canal and from the spatially complementary otolith [2]. Convergence of macular and canal inputs concern about 80% of tested vestibular neurons [3]. The anatomical convergence and functional complementarities between canals and otoliths raise questions on how spatial refinements of vestibular microcircuits at the origin of the vestibulo-ocular reflex (VOR) occur during development and adapt throughout lifespan. As for other developing systems, ontogeny of the vestibular system depends on both genetics and experience [5]. Late activity-mediated maturation would refine its function [9,10]
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