Disorders in balance and spatial perception, resulting from damage of the vestibular system, affect many Americans and are an important contributors to the overall cost of health care in this country. Treatment with aminoglycoside antibiotics such as streptomycin produces damage to the peripheral vestibular receptors and innervating afferents in humans and other animals. In recent years, regeneration of the damaged neuroepithelium and reinnervation of the newly formed receptor cells has been shown to occur. However, almost nothing is known about how vestibular mediated behavioral responses, such as the linear vestibulo-ocular reflexes (LVOR) functionally recover during the regeneration process. In order for the reflexes to recover, primary afferents must reinnervate the receptor neuroepithelium and establish functional connections. For the otolith organs, reinnervating afferents must re-establish directional selectivity and temporal response properties that are distributed correctly to produce the required compensatory eye movements. As regeneration progresses, are the response properties of reinnervating otolith afferents similar or different to those observed in normal animals? Do the otolith mediated behaviors like the LVOR return to normal function after regeneration of the macula is complete? One of the primary objectives of the current project is to first delineate the spatial and temporal response properties of utricular afferents during regeneration of the macula following treatment with ototoxic antibiotics. Two distinct time periods of regeneration will be examined, with extracellular single unit recordings in chronic pigeon preparations. The second major objective is to examine the return of LVOR function following ototoxic treatment. LVOR responses will be quantified by measuring three-dimensional eye movements before, acutely after (1 - 4 days), at an early period (7 - 21 days), and at a late period (120 - 150 days) of macula regeneration. Knowledge regarding the process of functional recovery of afferent responsiveness and compensatory reflexive eye movements during regeneration will be obtained. Before more effective treatments for balance disorders can be realized, insight into the nature of how animals function to maintain movement reflexes and recover from vestibular system damage is essential.
| 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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