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

摘要 视觉-运动转换和眼动的产生需要处理 同时发生在两个大脑半球。人们经常认为，不间断的 从一个半球到另一个半球的信息传输和竞争的解决方案 行动计划是微不足道的问题。然而，情况不太可能是这样，因为许多视觉运动 障碍与大脑半球间通信功能障碍有关，包括 斜视、弱视、忽视和癫痫。因此，半球间的通信是一种 研究不足，但大脑功能的核心部分。 同时从两个半球记录并识别准确的神经元的能力 传统上，它们之间的联系很难实现。然而，我们最近 开发了光遗传工具，可以可靠地定位和标记跨半球的输入到 特定的大脑区域。再加上记录神经元数量的现代技术，这 方法有望开启以灵长类为中心的研究的新时代，绘制大脑图谱 需要将两个半球的皮质活动结合起来的回路，以产生明确的 感知并计划一个具体的行动。 直接将大脑半球之间的神经元连接与其功能联系起来的能力 视觉-运动行为中的角色为研究长期存在的 假设特定运动矢量在一个半球的活动抑制不同 另一个是运动活动。我们提出了通过大写来检验这一假设的实验 关于眼动和眼球运动的特征、精确测量和自然主义的本质 额叶眼场(FEF)对大脑皮质的控制。在我们的第一个具体目标中，我们将通过光学 识别和激活记录时在一个FEF中投射到两个半球的神经元 从另一个FEF中的受体神经元来确定其中一个区域的活动是否增加 大脑半球减少具有不同方向偏好的受体神经元的活动 另一个半球。我们的第二个特定目标将使用类似的设置，但会抑制 跨半球皮质输入，以更彻底地测试管理 两个半球之间的交流。总的来说，拟议的实验将：1)识别大脑皮层 自然视觉和眼球运动期间的跨半球协调机制， 为今后的大脑半球间皮层通讯工作做好准备；2)建立精确的、 用于识别皮质输入的可靠工具，可极大地改进皮质回路的映射。

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.