Central pathways responsible for control of vestibular processes normally receive information about head movements encoded in the discharge properties of vestibular-nerve afferents innervating each labyrinth. Alteration of these inputs from vestibular end-organs on one side results in distorted vestibular reflexes and evokes mechanisms of compensation. The changes following unilateral vestibular lesions and the neurophysiological events mediating compensation are poorly understood. Behavioral and single-unit studies will be performed in alert squirrel monkeys to define mechanisms of compensation in angular vestibulo-ocular reflexes after each of two unilateral vestibular lesions. One lesion paradigm will involve unilateral mechanical inactivation of the three semicircular canals and the other will consist of unilateral labyrinthectomy with vestibular neurectomy. Canal plugging preserves the tonic discharge of vestibular-nerve afferents whereas labyrinthectomy with vestibular neurectomy results in a permanent ablation of all vestibular afferent activity on the lesioned side. These two vestibular lesions will be used to address three specific aims. I) The behavioral effects of each vestibular lesion on gain and symmetry of the angular horizontal and vertical vestibulo-ocular reflexes (VORs) will be studied in alert squirrel monkeys trained to fixate target lights and make smooth pursuit eye movements. The role of tonic vestibular afferent activity preserved after canal plugging in recovery of VOR gain and symmetry will be defined. 2) The firing characteristics of central vestibular neurons isolated in the vestibular nuclei will be recorded in alert, trained squirrel monkeys to determine the neurophysiological basis of changes observed in the VORs after each of the vestibular lesions. 3) The responses of central vestibular neurons to galvanic polarizations delivered through implanted labyrinthine stimulating electrodes will be studied. The role of vestibular inputs from the nonlesioned labyrinth in mechanisms of compensation after each of the two vestibular lesions will thereby be characterized. These studies will enhance our understanding of normal vestibular processes and contribute to defining processes of plasticity and adaptation in this system. Research described in this proposal is directly relevant to the diagnosis and treatment of vestibular disorders in humans.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC002390-05
Application #
6055823
Study Section
Hearing Research Study Section (HAR)
Project Start
1995-09-01
Project End
2000-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Eron, Julia N; Davidovics, Natan; Della Santina, Charles C (2015) Contribution of vestibular efferent system alpha-9 nicotinic receptors to vestibulo-oculomotor interaction and short-term vestibular compensation after unilateral labyrinthectomy in mice. Neurosci Lett 602:156-61
Sun, Daniel Q; Lehar, Mohamed; Dai, Chenkai et al. (2015) Histopathologic Changes of the Inner ear in Rhesus Monkeys After Intratympanic Gentamicin Injection and Vestibular Prosthesis Electrode Array Implantation. J Assoc Res Otolaryngol 16:373-87

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