The primate oculomotor system is a premier model system for understanding the production of reflexive and volitional movements. Two types of saccadic eye movements are made by humans and monkeys: regular and express saccades. Regular saccades have long latencies and are thought to involve the transfer of information from the visual cortex, to the frontal cortex, to the superior colliculus. Express saccades have shorter latencies and are thought to be mediated by a direct pathway from visual cortex to the superior colliculus, bypassing the frontal cortex. Importantly, under some conditions both express and regular saccades are made in roughly equal proportion; express saccades occur on some trials, regular saccades on other, seemingly identical, trials. If, as hypothesized, express saccades are mediated by projections from the visual cortex to the superior colliculus, the probability of express saccade occurrence should increase if these projections are stimulated under conditions in which they are not naturally strongly activated. Such a manipulation was technically impossible until recently, but optogenetics has changed this. Optogenetics is a relatively new set of tools for manipulating neural activity with light, an these tools have already been extremely valuable in the study of transgenic mice. By using these tools in the awake, behaving primate, two specific aims and one broader objective will be achieved.
The first aim i s to test the hypothesis that the projections from visual cortex to the superior colliculus facilitate express saccades.
The second aim i s to test the hypothesis that electrical activity between two usually disconnected compartments in the superior colliculus become transiently connected during express saccades. The larger objective is to catalyze progress in systems neurophysiology by refining optogenetic tools for use in the awake, behaving monkey. Widespread adoption and refinement of these techniques by the primate neurophysiology community will help to reveal how signal transmission between brain areas mediates behavior. Such an understanding will be important for the diagnosis and treatment of neurological and psychiatric diseases, whose etiology may involve aberrant communication between brain areas.

Public Health Relevance

Understanding how signals from one area of the brain to another influence behavior is an important step towards effective treatments for neurological and psychiatric diseases which may involve a functional disconnection between areas. The proposed experiments use an emerging technology to manipulate signals between two areas of the primate brain that participate in eye movements. Revealing how signal transmission between these areas contributes to the control of eye movements will bring us a step closer to understanding how connections between brain areas contribute to behavior more generally.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21EY024362-02
Application #
8822876
Study Section
Special Emphasis Panel (ZRG1-SPC-T (09))
Program Officer
Araj, Houmam H
Project Start
2014-04-01
Project End
2016-03-31
Budget Start
2015-04-01
Budget End
2016-03-31
Support Year
2
Fiscal Year
2015
Total Cost
$218,050
Indirect Cost
$95,550
Name
University of Washington
Department
Physiology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Galvan, Adriana; Stauffer, William R; Acker, Leah et al. (2017) Nonhuman Primate Optogenetics: Recent Advances and Future Directions. J Neurosci 37:10894-10903
El-Shamayleh, Yasmine; Kojima, Yoshiko; Soetedjo, Robijanto et al. (2017) Selective Optogenetic Control of Purkinje Cells in Monkey Cerebellum. Neuron 95:51-62.e4