| Task Description: |
POSTDOCTORAL FELLOWSHIP.
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: 1) "disorientation and inability to perform landing, egress, or other physical tasks, especially during/after g-level changes", and 2) "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 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 to understand the early and long term effects of altered gravity on the function of its primary receptors, the utricular hair cells.
|
| Research Impact/Earth Benefits: |
This basic research on the synaptic vesicle cycle and exocytosis in vestibular hair cells is being investigated in normal and hypergravity. This study will give new insights on the normal functioning of hair cells and synaptic ribbons. As in any basic research, such knowledge should help any applied research to find a treatment or prevention for vestibular dysfunction, for example, vertigo. |
Developed and operated by: NASA Research and Education Support Services
