Over the past decade it has been well established that lost vestibular hair cells regenerate and are re-innervated. Although some information on vestibular responses during regeneration has been obtained, much remains to be learned regarding the functional recovery of compensatory neuromotor behaviors and their underlying neural mechanisms. We have recently developed a method for administration of streptomycin that results in complete hair cell loss and afferent denervation of the vestibular organs in adult pigeons at a discrete point in time. We have used the method to identify three separate stages of vestibular regeneration, where different morphological characteristics of hair cell distribution and afferent innervation were observed. We now propose to use the method to study the regenerative development of vestibular function. Our investigations will focus upon the recovery of afferents, central vestibulospinal neurons and gaze behavior during regeneration. The working conceptual framework is that a specific progression in vestibular neuromotor behaviors and the neuronal physiological responses that comprise them will occur during regeneration, as correlated to the three morphological stages of peripheral development. Both behavioral and physiological studies in alert pigeons will be used to test specific hypotheses derived from our conceptual framework. First, we will characterize the development of vestibular afferent responses during regeneration. The spatial tuning and response dynamics of afferents will be examined longitudinally during re-innervation of the vestibular receptors. Second, we will characterize the development of central vestibulospinal neuronal responses during regeneration. Third, we will characterize the compensatory eye and gaze responses in head free birds during regeneration. Increasing our fundamental understanding of the processes underlying regeneration recovery is essential before more effective treatments of vestibular system disorders can be realized. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC003286-09
Application #
6734151
Study Section
Special Emphasis Panel (ZRG1-IFCN-6 (01))
Program Officer
Platt, Christopher
Project Start
1998-01-01
Project End
2006-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
9
Fiscal Year
2004
Total Cost
$348,075
Indirect Cost
Name
Washington University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
McArthur, K L; Zakir, M; Haque, A et al. (2011) Spatial and temporal characteristics of vestibular convergence. Neuroscience 192:361-71
Huss, David; Navaluri, Rena; Faulkner, Kathleen F et al. (2010) Development of otolith receptors in Japanese quail. Dev Neurobiol 70:436-55
Haque, Asim; Zakir, Mridha; Dickman, J David (2009) Regeneration of vestibular horizontal semicircular canal afferents in pigeons. J Neurophysiol 102:1274-86
Haque, Asim; Zakir, Mridha; Dickman, J David (2008) Recovery of gaze stability during vestibular regeneration. J Neurophysiol 99:853-65
Zakir, Mridha; Dickman, J David (2006) Regeneration of vestibular otolith afferents after ototoxic damage. J Neurosci 26:2881-93
Haque, Asim; Huss, David; Dickman, J David (2006) Afferent innervation patterns of the pigeon horizontal crista ampullaris. J Neurophysiol 96:3293-304
Haque, Asim; Dickman, J David (2005) Vestibular gaze stabilization: different behavioral strategies for arboreal and terrestrial avians. J Neurophysiol 93:1165-73
Dickman, J David; Huss, David; Lowe, Melissa (2004) Morphometry of otoconia in the utricle and saccule of developing Japanese quail. Hear Res 188:89-103
Dickman, J David; Lim, Insook (2004) Posture, head stability, and orientation recovery during vestibular regeneration in pigeons. J Assoc Res Otolaryngol 5:323-36
Zakir, M; Huss, D; Dickman, J D (2003) Afferent innervation patterns of the saccule in pigeons. J Neurophysiol 89:534-50

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