Optogenetic dissection of inter-hemispheric frontal eye field circuits for eye movements

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Abstract Visual-motor transformations and the generation of eye movements require processing that occurs in both brain hemispheres simultaneously. It is often assumed that the uninterrupted transfer of information from one hemisphere to the other and the resolution of competing movement plans are trivial problems. Yet this is unlikely the case because many visual-motor disorders have been linked to dysfunctions in inter-hemispheric communication, including strabismus, amblyopia, neglect, and epilepsy. Thus, inter-hemispheric communication is an understudied but central part of brain function. The ability to record from both hemispheres simultaneously and identify the exact neuronal connections between them has traditionally been difficult to accomplish. However, we recently developed optogenetic tools that reliably locate and label the cross-hemisphere inputs to a particular brain region. Coupled with modern techniques for recording neuronal populations, this approach promises to usher in a new era of primate-centric research that maps the brain circuitry needed to combine cortical activity in both hemispheres to generate an unambiguous percept and plan a specific action. The ability to directly link neuronal connections between brain hemispheres with their functional role in visual-motor behavior provides a powerful tool for investigating the longstanding hypothesis that activity for a specific movement vector in one hemisphere inhibits dissimilar movement activity in the other. We propose experiments that test this hypothesis by capitalizing on the well-characterized, precisely measurable, and naturalistic nature of eye movements and their cortical control by the frontal eye fields (FEF). In our first specific aim, we will optically identify and activate neurons in one FEF that project across the hemispheres while recording from recipient neurons in the other FEF to determine whether increased activity in one hemisphere decreases the activity of recipient neurons with dissimilar direction preferences in the other hemisphere. Our second specific aim will use a similar setup but inhibit the activity of cross-hemisphere cortical inputs to more thoroughly test the network architecture that governs inter-hemispheric communication. Collectively, the proposed experiments will: 1) identify cortical mechanisms for cross-hemispheric coordination during natural vision and eye movements, in preparation for future work on interhemispheric cortical communication; 2) establish a precise, reliable tool for identifying cortical inputs to greatly improve the mapping of cortical circuitry.