Disruption of vestibular signals from one labyrinth results in asymmetries in the angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration head movements. Studies during the previous funding period have elucidated linear and nonlinear components of the angular VOR in the squirrel monkey, demonstrated selective adaptation of these components with magnifying or minimizing spectacles, compared the horizontal angular VOR in squirrel monkeys and macaques in response to rapid rotations, defined the response properties of vestibular-nerve afferents to rapid head rotations, and analyzed changes in the angular VOR, afferents, and hair cells following unilateral ototoxic vestibular injury with gentamicin. The proposed research builds upon previous accomplishments through studies that are organized into three specific aims. The experiments are performed in chinchillas and in macaques. Studies in Aim I will define the responses of vestibular-nerve afferents to steps of acceleration and study the contributions of irregularly discharging afferents to the horizontal VOR evoked by these rapid head rotations. Bilateral, anodal galvanic currents delivered to each labyrinth will be used to substantially attenuate or silence irregular afferents during rapid head rotations. The experiments that are conducted in macaques will involve analysis of the normal VOR as well as following spectacle-induced adaptation.
Aim II will investigate the contribution to VOR compensation of preserved resting rate in afferents on the side of a unilateral vestibular lesion and of afferents from the contralesional (intact) labyrinth. The unilateral lesion that preserves resting rate but abolishes or markedly attenuates responses to motion involves intratympanic injection of gentamicin.
Aim III will examine neural correlates of compensatory changes in the horizontal VOR in macaques after unilateral labyrinthectomy. These experiments will determine if the discharge properties of vestibular-nerve afferents on the contralateral side change following unilateral labyrinthectomy. The dynamics of vestibular nuclei neurons that mediate the VOR will be studied following unilateral labyrinthectomy. The role of proprioceptive inputs and anticipatory mechanisms in modifying the responses of these central neurons will be determined by comparing neuronal responses during actively and passively generated head-on-body and whole-body rotations.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC002390-13
Application #
7268730
Study Section
Special Emphasis Panel (ZRG1-IFCN-A (90))
Program Officer
Platt, Christopher
Project Start
1995-09-01
Project End
2010-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
13
Fiscal Year
2007
Total Cost
$443,113
Indirect Cost
Name
Johns Hopkins University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Carriot, Jérome; Jamali, Mohsen; Cullen, Kathleen E et al. (2017) Envelope statistics of self-motion signals experienced by human subjects during everyday activities: Implications for vestibular processing. PLoS One 12:e0178664
Carriot, Jérome; Jamali, Mohsen; Chacron, Maurice J et al. (2017) The statistics of the vestibular input experienced during natural self-motion differ between rodents and primates. J Physiol 595:2751-2766
Mitchell, Diana E; Della Santina, Charles C; Cullen, Kathleen E (2017) Plasticity within excitatory and inhibitory pathways of the vestibulo-spinal circuitry guides changes in motor performance. Sci Rep 7:853
Mitchell, Diana E; Della Santina, Charles C; Cullen, Kathleen E (2016) Plasticity within non-cerebellar pathways rapidly shapes motor performance in vivo. Nat Commun 7:11238
Jamali, Mohsen; Chacron, Maurice J; Cullen, Kathleen E (2016) Self-motion evokes precise spike timing in the primate vestibular system. Nat Commun 7:13229
Straka, Hans; Zwergal, Andreas; Cullen, Kathleen E (2016) Vestibular animal models: contributions to understanding physiology and disease. J Neurol 263 Suppl 1:S10-23
Rabbitt, Richard D; Brichta, Alan M; Tabatabaee, Hessam et al. (2016) Heat pulse excitability of vestibular hair cells and afferent neurons. J Neurophysiol 116:825-43
Jayabal, Sriram; Chang, Hui Ho Vanessa; Cullen, Kathleen E et al. (2016) 4-aminopyridine reverses ataxia and cerebellar firing deficiency in a mouse model of spinocerebellar ataxia type 6. Sci Rep 6:29489
Carriot, Jerome; Jamali, Mohsen; Brooks, Jessica X et al. (2015) Integration of canal and otolith inputs by central vestibular neurons is subadditive for both active and passive self-motion: implication for perception. J Neurosci 35:3555-65
Cullen, Kathleen E; Brooks, Jessica X (2015) Neural correlates of sensory prediction errors in monkeys: evidence for internal models of voluntary self-motion in the cerebellum. Cerebellum 14:31-4

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