The vestibulo-ocular (VORs) are an essential component of the oculomotor system since they are fundamental for gaze stabilization during both angular (angular VORs) and linear (linear VORs) head movements. Damage to the vestibular system through disease or trauma can produce profound oculomotor deficits that are often difficult to resolve clinically. Vestibular disturbances are often accompanied by nystagmus, blurred vision, dizziness and spatial disorientation. Despite years of research regarding the neural mechanisms of angular VOR function and disease states, very little is currently known about the linear VORs. Moreover, almost no information exists regarding the symptomology of otolith system damage and few, if any, practical diagnostic evaluations of otolith function are routinely performed in clinical today. The current proposal seeks to study the nature and function of the linear VORFs in primates and to investigate the deficits produced by cerebellar lesions and peripheral vestibular damage. The primary goal of these studies is to test quantitative predictions of a functional framework regarding the bilateral organization of the linear VORs across a wide stimulus repertoire in awake rhesus monkeys trained to fixate targets at different distances and vertical/horizontal eccentricities. Precisely calibrated binocular three-dimensional eye movements will be recorded during both lateral and fore-act linear motion consisting of either steady-state sinusoidal or transient stimulus profiles. Data obtained from normal animals will be quantitatively compared to the eye movements generated during functional ablation of the most irregularly firing vestibular afferents, as well as both acutely and chronically after unilateral labyrinthectomy, selective semicircular canal plugging and cerebellar lesions. The results will provide for the first time quantitative data and models regarding the bilateral neural organization of the linear VORs as well as identify practical clinical tests of peripheral and central otolith-ocular function.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Visual Sciences B Study Section (VISB)
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Hunter, Chyren
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Washington University
Anatomy/Cell Biology
Schools of Medicine
Saint Louis
United States
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Laurens, Jean; Liu, Sheng; Yu, Xiong-Jie et al. (2017) Transformation of spatiotemporal dynamics in the macaque vestibular system from otolith afferents to cortex. Elife 6:
Laurens, Jean; Kim, Byounghoon; Dickman, J David et al. (2016) Gravity orientation tuning in macaque anterior thalamus. Nat Neurosci 19:1566-1568
Meng, Hui; Laurens, Jean; Blázquez, Pablo M et al. (2015) In vivo properties of cerebellar interneurons in the macaque caudal vestibular vermis. J Physiol 593:321-30
Blazquez, Pablo M; Yakusheva, Tatyana A (2015) GABA-A Inhibition Shapes the Spatial and Temporal Response Properties of Purkinje Cells in the Macaque Cerebellum. Cell Rep 11:1043-53
Meng, Hui; Blázquez, Pablo M; Dickman, J David et al. (2014) Diversity of vestibular nuclei neurons targeted by cerebellar nodulus inhibition. J Physiol 592:171-88
Laurens, Jean; Meng, Hui; Angelaki, Dora E (2013) Computation of linear acceleration through an internal model in the macaque cerebellum. Nat Neurosci 16:1701-8
Van Dijck, Gert; Van Hulle, Marc M; Heiney, Shane A et al. (2013) Probabilistic identification of cerebellar cortical neurones across species. PLoS One 8:e57669
Liu, Sheng; Gu, Yong; DeAngelis, Gregory C et al. (2013) Choice-related activity and correlated noise in subcortical vestibular neurons. Nat Neurosci 16:89-97
Laurens, Jean; Meng, Hui; Angelaki, Dora E (2013) Neural representation of orientation relative to gravity in the macaque cerebellum. Neuron 80:1508-18
Yakusheva, Tatyana A; Blazquez, Pablo M; Chen, Aihua et al. (2013) Spatiotemporal properties of optic flow and vestibular tuning in the cerebellar nodulus and uvula. J Neurosci 33:15145-60

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