Our visual system is specialized for central vision, which is served by the foveal region of the retina. High- acuity vision is possible only when the visual world is kept relatively stable on the retina. Visual image stability is preserved during head movements by the compensatory action of the vestibular ocular (VOR) and optokinetic reflexes (OKR). When an object of interest moves relative to the head, the VOR needs to be adjusted to maintain tracking. This adjustment is accomplished, in part, by the smooth pursuit (SP) system. Foveal SP is primarily a volitional behavior, which depends on processing of visual and eye movement information in cerebral cortex, brainstem and cerebellum. There are multiple pathways leaving frontal and parietal cortical areas, which contribute differentially to SP and visual-vestibular behavior. The long-term goal of our studies is to determine the specific SP-related information represented in parallel frontal- and parietal- brainstem pathways. Our proposed studies are designed to determine neural mechanisms responsible for converting visual motion information into commands for eye movements during different SP behaviors. Our overarching hypothesis is that the information processed in each parallel cortical-brainstem pathway differentially supports different aspects of SP including prediction, initiation, maintenance, gain control and adaptive modification. To test our hypothesis, projection neurons in FEF and MST cortex are identified using antidromic activation following delivery of electrical stimulation pulses in SP regions of the brainstem. We then use computational methods to compare and contrast the information carried in activated neurons located in layer-5 with non-activated neurons in other cortical layers. The significance of our work is that SP is compromised in different developmental or disease processes. Therefore, our studies are designed to test real SP circuits in a manner that will aid in the diagnosis and potential treatment of disorders associated with strabismus, neurodegenerative disease, brain injury and stroke.

Public Health Relevance

We use eye and head movements to direct the line of sight so that objects of interest, whether stationary or moving, are imaged on the fovea of each eye. Damage to the cortical smooth pursuit system and distal circuits involving the brainstem and cerebellum results in loss of visual, vestibular and oculomotor function. Advancing our understanding of how signals are processed in parallel cortical-brainstem pathways could lead to improved diagnosis and treatment options for developmental disorders such as strabismus and acquired disorders associated with brain injury, neurodegenerative disease and stroke.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY013308-12
Application #
8607947
Study Section
Special Emphasis Panel (ZRG1-IFCN-N (02))
Program Officer
Araj, Houmam H
Project Start
2000-12-01
Project End
2017-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
12
Fiscal Year
2014
Total Cost
$324,405
Indirect Cost
$142,155
Name
University of Washington
Department
None
Type
Other Domestic Higher Education
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Brostek, Lukas; B├╝ttner, Ulrich; Mustari, Michael J et al. (2015) Eye Velocity Gain Fields in MSTd During Optokinetic Stimulation. Cereb Cortex 25:2181-90
Walton, Mark M G; Mustari, Michael J; Willoughby, Christy L et al. (2015) Abnormal activity of neurons in abducens nucleus of strabismic monkeys. Invest Ophthalmol Vis Sci 56:9-Oct
Ono, Seiji; Mustari, Michael J (2012) Role of MSTd extraretinal signals in smooth pursuit adaptation. Cereb Cortex 22:1139-47
Lienbacher, Karoline; Mustari, Michael; Ying, Howard S et al. (2011) Do palisade endings in extraocular muscles arise from neurons in the motor nuclei? Invest Ophthalmol Vis Sci 52:2510-9
Ono, Seiji; Brostek, Lukas; Nuding, Ulrich et al. (2010) The response of MSTd neurons to perturbations in target motion during ongoing smooth-pursuit eye movements. J Neurophysiol 103:519-30
Schreyer, S; Buttner-Ennever, J A; Tang, X et al. (2009) Orexin-A inputs onto visuomotor cell groups in the monkey brainstem. Neuroscience 164:629-40
Mustari, Michael J; Ono, Seiji; Das, Vallabh E (2009) Signal processing and distribution in cortical-brainstem pathways for smooth pursuit eye movements. Ann N Y Acad Sci 1164:147-54
Ono, Seiji; Mustari, Michael J (2009) Smooth pursuit-related information processing in frontal eye field neurons that project to the NRTP. Cereb Cortex 19:1186-97
Ono, Seiji; Mustari, Michael J (2008) Role of the MST-DLPN pathway in smooth pursuit adaptation. Prog Brain Res 171:161-5
Ono, Seiji; Mustari, Michael J (2006) Extraretinal signals in MSTd neurons related to volitional smooth pursuit. J Neurophysiol 96:2819-25

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