DESCRIPTION (provided by applicant): Gravity receptor organs of the vestibular system (i.e. the maculae) detect, encode and send to the brain information about head position as well as the magnitude and direction of head movements in relation to Earth's gravitational field. The brain uses this information to maintain postural balance and proper spatial orientation. Each gravity receptor neuron generally innervates many receptor cells (hair cells) and together the neuron and innervated hair cells comprise a macular sensory unit (SU). Each hair cell responds best to linear acceleration stimuli in a particular direction based upon the orientation of its stereociliary bundle. The orientation of the steriociliary bundle is called the morphological polarization vector (MPV). Hair cells are collectively arranged to form a highly organized MPV map on the macular surface. Each SU can provide remarkable directional specificity, which forms the basis for spatial coding. Not clear is how neurons manage to find and secure hair cells with nearly the same MPVs during development thereby ensuring the formation of a refined spatial code. We hypothesize (1) that a process exists, which drives SU field refinements during development to produce SUs that incorporate hair cells that respond best to stimuli of nearly the same direction. We also hypothesize (2) that a stimulus-independent process determines the organization of the macular MPV map whereas SU field refinements are strictly dependent upon natural stimulation of gravity receptors. Our Specific Aim is to test these hypotheses by determining the ontogeny of the utricular MPV map and SU fields 1) in normal mice and 2) in mice where the utriculus is deprived of natural stimulation (i.e. in otoconia-deficient mice: head tilt (bet) and tilted (tlt)). The macular MPV maps and SU fields for ages E 13-E 15, E 16-E 17, E 17-E 18, P 1-P4, P7-P 10 & P28 will be characterized. Confocal microscopy will be used to document the receptive fields of macular afferents and the MPVs of associated hair cells. Regional synaptic ribbon densities will also be determined. The spontaneous activity of macular SUs will be characterized at P5-P 14 & P28 in order to clarify the physiological status of gravity receptors in otoconia deficient mice. The proposed research will examine the role of natural stimulation in normal gravity receptor ontogeny. Understanding the ontogeny of gravity reception and mechanisms controlling it will help provide the basis for identifying factors that can affect development and produce abnormal growth and function.
|Effective start/end date||9/1/03 → 8/31/09|
- National Institutes of Health: $362,624.00
- National Institutes of Health: $279,883.00
- National Institutes of Health: $133,405.00
- National Institutes of Health: $376,806.00
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