期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：46
页码：E7297-E7306
DOI：10.1073/pnas.1610784113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThe frontal eye field (FEF) is critical for making eye movements to remembered locations. FEF neurons increase their firing rate in response to seeing a target, to remembering the target location during a delay period, and to planning eye movements to the location. Conventional tools do not allow us to determine what aspects of FEF neuronal activity (i.e., visual, delay, motor) are critical for memory-guided eye movements, so we developed optogenetic tools to inactivate FEF neurons during each task epoch individually. We found that all aspects of FEF firing contribute to behavior. Further, we present tools that inactivate large enough brain volumes for optogenetics to be widely used in primate neuroscience and, potentially, human medicine. Optogenetic methods have been highly effective for suppressing neural activity and modulating behavior in rodents, but effects have been much smaller in primates, which have much larger brains. Here, we present a suite of technologies to use optogenetics effectively in primates and apply these tools to a classic question in oculomotor control. First, we measured light absorption and heat propagation in vivo, optimized the conditions for using the red-light-shifted halorhodopsin Jaws in primates, and developed a large-volume illuminator to maximize light delivery with minimal heating and tissue displacement. Together, these advances allowed for nearly universal neuronal inactivation across more than 10 mm3 of the cortex. Using these tools, we demonstrated large behavioral changes (i.e., up to several fold increases in error rate) with relatively low light power densities ([≤]100 mW/mm2) in the frontal eye field (FEF). Pharmacological inactivation studies have shown that the FEF is critical for executing saccades to remembered locations. FEF neurons increase their firing rate during the three epochs of the memory-guided saccade task: visual stimulus presentation, the delay interval, and motor preparation. It is unclear from earlier work, however, whether FEF activity during each epoch is necessary for memory-guided saccade execution. By harnessing the temporal specificity of optogenetics, we found that FEF contributes to memory-guided eye movements during every epoch of the memory-guided saccade task (the visual, delay, and motor periods).
