Space motion sickness is the earliest impairment experienced by humans in microgravity, and results in orientation and balance impairments. To research possible countermeasures, NSBRI Postdoctoral Fellow Dr. Sophie Gaboyard is studying the mechanisms that affect adaptation to microgravity and its early- and long-term effects at the cellular level by looking at neurotransmission in the vestibular hair cells of rodents. Using centrifugation to vary gravity, Gaboyard will chronicle synaptic transmission of vestibular hair cells at specific time intervals and investigate whether altered gravity affects early gene expression.
Overview
Adaptation of Rodent Vestibular Hair Cell Neurotransmission in Altered Gravity (Postdoctoral Fellowship)
Principal Investigator:
Sophie Gaboyard, Ph.D.
Organization:
University of Illinois
Technical Summary
Space motion sickness is the earliest impairment experienced by humans in altered gravity. It is an important problem since it severely alters performance of affected astronauts. We propose to study the early mechanisms that can affect the adaptation of mammalian vestibular hair cells in altered gravity. All specific aims will focus on utricular hair cell neurotransmission in mice.
The first aim will provide an overview of synaptic transmission by looking at the vesicle recycling rates in utricle submitted to hypergravity over time. The second correlated aim will attempt to understand the time scale of molecular mechanisms that can sustain the modification of hair cell neurotransmission in hypergravity. Both aims will provide a time scale of the early modifications that can occur in primary gravity receptors undergoing altered stimulation. The last aim of this project is to study the functional capabilities of adult utricular hair cells whose development occurred under conditions of sensory deprivation. This last ground-based experiment will use a mammalian "weightlessness" model, the tilted mouse. This last aim will provide some insight about the risks of developing organisms in space.
These objectives are directly relevant to different goals of the NSBRI Neurovestibular Adaptation team since they can lead to the development of countermeasures to limit the risk of:
- Disorientation and inability to perform landing, egress or other physical tasks, especially during/after g-level changes", and;
- Possible chronic impairments of orientation or balance function due to microgravity.
Centrifugation will be used to submit mice to hypergravity. Their utricular maculae will be studied using immunofluorescent staining, imaging, deconvolution and three-dimensional (3D) reconstruction. A precise map of synaptic transmission, through vesicle recycling staining (AM 1-43), and the numbers of ribbons (Ribeye) and synaptic vesicles (Rab 3A, RIM 1) will be provided for 2, 6 and 8 hours of hyperstimulation. The nitric oxide pathway and its relation to immediate early gene expression will also be investigated in utricular hair cells during these time-exposures to hypergravity.
Investigations of these same proteins and vesicle recycling in utricular hair cells of tilted mice will determine their functional capabilities. Thus, this project will help us understand the early and long-term effects of altered gravity on the function of its primary receptors, the utricular hair cells.
Earth Applications
This basic research in normal gravity and in a microgravity model of vestibular sensory deprivation gave new insights on the development and adult physiology of hair cells. Studies of Na+ and K+ voltage-dependent channels determined their precise patterns of expression in vestibular sensory epithelium from birth to adult with direct relevance to the normal functioning of hair cells (Wooltorton et al., 2006; Hurley et al., 2006; Gaboyard et al., in preparation).
Lipofuscin-like organelles were investigated and quantified in hair cells of rodents in normal environmental conditions, giving new insights on their potential link to aging and ototoxicity (Gaboyard and Lysakowski, in preparation). Morphological and molecular properties of macular hair cells were determined in a rodent model of sensory deprivation that corresponds to a micro-gravitational environment.
This study showed that hair cells developed and living in a micro-gravitational environment display normal properties to function properly in normal gravity; this suggests a capacity of the vestibule to develop and survive in different gravitational environments (Gaboyard, in preparation).
This project's funding ended in 2006