Exposure to microgravity causes postural, locomotor and oculomotor modifications. In order to realize long term space flight, effective countermeasures for these abnormalities must be developed. Toward this end, it is essential to understand the cellular and biological basis underlying centrally-mediated vestibular adaptation to altered gravity conditions. The objective of the proposed research is to identify the morphologic alterations in rat cerebellar cortex that correlate with sensory and motor adaptation to microgravity. The investigators propose ground- based and space- based studies to test the hypotheses that (a) ultrastructural alterations accompany adaptation to microgravity, and (b) such alterations are pathway and neurotransmitter-specific. The merit of this idea has been emphasized in several brief communications by Krasnov and co-workers, in which ultrastructural changes in Purkinje cell synaptology have been reported in the nodulus of rats following spaceflight. These observations are of particular interest because Purkinje cells in the nodulus control habituation of the vestibulo- ocular reflex, and are likely to be critical for maintaining spatial orientation with regard to gravity. In addition, physiologic investigations have clearly indicated a role for the flocculus in controlling specific aspects of the VOR. The investigators propose to study the cerebellar cortex from (1) brain tissue already processed in the laboratory from flight and control rats of PARE.0.2 from the STS-54 shuttle mission; (2) flight and control rats from the Neurolab shuttle mission; and (3) naive laboratory rats. The tissue will be used for quantitative ultrastructural and immunocytochemical studies of synaptic circuits in the nodulus and ventral uvula, flocculus and paraflocculus, and non-vestibular cerebellar cortex. The investigators expect to obtain stereological data supporting a change in synaptology in vestibular, but not in non-vestibular cerebellum of flight rats. The qualitative and/or quantitative differences in excitatory amino acid and GABAergic neurotransmission in the nodulus and flocculus of flight rats will also be compared to controls and naive animals. The investigators expect to obtain critical information about the alterations in synaptology and neurotransmitter localization in the nodulus and flocculus that accompany adaptation to microgravity. The identification and characterization of GABAergic and GABA-receptive elements in this paradigm should lead to a greater understanding of how inhibition is modified in neuronal circuits during behavioral adaptation. Similarly, delineation of the microgravity-induced alterations in excitatory glutamatergic transmission will contribute to our basic knowledge of the morphologic basis for cerebellar-mediated motor learning. Through comparison of tissue from ground-based rats with animals sacrificed postflight and animals sacrificed during flight, it will be possible to localize, characterize and quantify the site(s) and synapses that mediate vestibular adaptation phenomena in space.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project--Cooperative Agreements (U01)
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Mount Sinai School of Medicine
Schools of Medicine
New York
United States
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Cohen, Bernard; Yakushin, Sergei B; Holstein, Gay R et al. (2005) Vestibular experiments in space. Adv Space Biol Med 10:105-64
Holstein, G R; Kukielka, E; Martinelli, G P (1999) Anatomical observations of the rat cerebellar nodulus after 24 hr of spaceflight. J Gravit Physiol 6:P47-50
Holstein, G R; Martinelli, G P; Cohen, B (1999) Ultrastructural features of non-commissural GABAergic neurons in the medial vestibular nucleus of the monkey. Neuroscience 93:183-93