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

用于眼球运动的半球间额眼场回路的光遗传学解剖

基本信息

批准号：
10707079
负责人：
Joseph Patrick Mayo
金额：
$ 19.93万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-30 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10707079
关键词：
Amblyopia American Anatomy Behavior Behavioral Brain Brain Mapping Brain region Cerebral hemisphere Cognition Communication Consensus Coupled Disease Disinhibition Dissection Dissociation Epilepsy Eye Movements Failure Foundations Functional disorder Future Generations Goals Intervention Label Left Light Link Maps Measurable Measures Mediating Modernization Movement Nature Neurons Ocular Prosthesis Opsin Optics Outcome Pathologic Pathway interactions Physiological Physiology Play Population Prefrontal Cortex Preparation Primates Prosthesis Research Resolution Role Signal Transduction Source Strabismus Techniques Testing Transfection Viral Virus Vision Visual Work behavioral outcome brain circuitry clinical development control theory cortex mapping experimental study extracellular frontal eye fields functional magnetic resonance imaging/electroencephalography improved in vivo microstimulation motor behavior motor disorder neglect network architecture neural neuromechanism neurophysiology nonhuman primate oculomotor optogenetics personalized therapeutic preference response tool vector visual motor

项目摘要

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.

抽象的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中。通常假定不间断将信息从一个半球转移到另一个半球和竞争的解决运动计划是微不足道的问题。但事实不太可能，因为许多视觉运动疾病已与半球间交流中的功能障碍有关，包括斜视，弱视，忽视和癫痫病。因此，半球间的交流是研究了大脑功能的核心部分。同时从两个半球记录并识别精确神经元的能力传统上，他们之间的联系很难实现。但是，我们最近开发了光遗传学工具，可可靠地定位和标记交叉半球输入特定的大脑区域。再加上用于记录神经元种群的现代技术，方法有望引入以灵长类动物为中心的研究的新时代，该研究绘制了大脑在两个半球中结合皮质活性所需的电路才能产生明确的感知并计划特定的行动。将脑半球之间的神经元连接与功能直接连接神经元连接的能力在视觉运动行为中的角色为研究长期存在提供了强大的工具假设一个半球中特定运动载体的活性抑制不同另一个运动活动。我们提出了通过资本化检验该假设的实验关于眼睛运动的良好特征，精确的可测量和自然主义的性质他们通过额眼田（FEF）的皮质控制。在我们的第一个特定目标中，我们将光学在记录时识别并激活一个跨半球的FEF中的神经元来自另一个FEF中的接受者神经元，以确定一个人的活动是否增加半球降低了受体神经元具有不同方向偏好的活性另一半球。我们的第二个特定目标将使用类似的设置，但抑制跨半球皮质输入，以更彻底测试控制的网络体系结构半球间的交流。共同提议的实验将：1）识别皮质在自然视觉和眼睛运动过程中的跨斜膜协调的机制，为未来的妇女间皮质交流做准备； 2）确定一个确切的可靠的工具，用于识别皮质输入以极大地改善皮质电路的映射。