The oculomotor control system of foveate animals such as primates faces very diverse demands depending on the eye movement task. During some periods of time, the brain must precisely control the extraocular muscles so the eyes steadily fixate and stabilize the retinal image;during other periods, it must control the extraocular muscles to move the eyes rapidly from one position to another (saccades), or track objects of interest at widely differing speeds (smooth pursuit), or precisely change the viewing angle of the two eyes (vergence). It is currently assumed that these eye movements are produced through common pools of motor units (a "motor unit" is a motor neuron and its muscle fibers), recruited irrespective of task. But there is clear anatomic and histological evidence of motor unit diversity with physiological evidence of differential inputs from the oculomotor subsystems. Also, by directly measuring eye muscle forces using muscle force transducers (MFTs) and finding that they could not be predicted from neural innervation, we recently demonstrated that the simple concept of a final common motor path is incorrect ("missing force paradox"), and that this notion likely has impaired our understanding of the neuromuscular control of eye movements. In non-human primates, we propose to investigate how motor units with distinct characteristics and locations are recruited differentially for different horizontal ee motor tasks (saccades, smooth pursuit, and vergence) and task phases (phasic and tonic). We will identify lateral and medial rectus motoneurons using antidromic activation and spike-triggered averaging of electromyograms (STA-EMG), and measure motor unit functional properties using spike-triggered averaging of the muscle force transducer signal (STA-MFT), a new method we have recently validated. We will precisely localize motoneurons with X-ray images registered to MRI and histology, and fully characterize motor unit activity during these horizontal eye movements. Better understanding of eye motor control should lead to better treatment of eye movement disorders, such as strabismus. Drugs that modify eye muscle properties, elsewhere under development, show promise as simple, inexpensive office procedures able to effect corrections not possible with strabismus surgery. Our STA- MFT technique would be suitable to study the fiber type specific functionality of pharmacologically-modified motor units in alert animals. Relevance The novel techniques used in this proposal will allow us, for the first time, to study long-overlooked task specificities in the neuromuscular systems that stabilize and move our eyes for effective vision. These studies should result in more effective and less costly treatments for strabismus and other eye movement disorders that are of a neuromuscular origin.

Public Health Relevance

Accurate binocular alignment of the eyes on targets at different distances requires precise horizontal eye movements. Individuals with deficits in such eye movements are often strabismic and report diplopia (double-vision). We hypothesize that physiologically distinct motor unit types contribute differentially to the dynamic and static components of different horizontal eye movements. We will characterize such motor units in alert, behaving animals during different horizontal eye movements and hence test our hypothesis.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
3R01EY022290-01A1S2
Application #
8652536
Study Section
Special Emphasis Panel (ZRG1-IFCN-Q (03))
Program Officer
Araj, Houmam H
Project Start
2012-08-01
Project End
2017-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
1
Fiscal Year
2013
Total Cost
$11,134
Indirect Cost
$3,534
Name
University of Alabama Birmingham
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Bolding, Mark S; Lahti, Adrienne C; White, David et al. (2014) Vergence eye movements in patients with schizophrenia. Vision Res 102:64-70