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：
10527512
负责人：
Joseph Patrick Mayo
金额：
$ 24.92万
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/10527512
关键词：
Amblyopia American Anatomy Behavior Behavioral Brain Brain region Cerebral hemisphere Cognition Communication Consensus Coupled Disease Disinhibition Dissection 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 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 neuromechanism neurophysiology nonhuman primate oculomotor optogenetics personalized therapeutic preference relating to nervous system 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球运动的产生需要处理同时发生在两个大脑半球。人们通常认为不间断的信息从一个半球转移到另一个半球以及解决竞争问题运动计划是微不足道的问题。然而这种情况不太可能发生，因为许多视觉运动疾病与半球间沟通功能障碍有关，包括斜视、弱视、忽视和癫痫。因此，半球间的交流是一种尚未得到充分研究，但却是大脑功能的核心部分。能够同时记录两个半球并识别准确的神经元传统上，它们之间的联系很难实现。然而，我们最近开发了光遗传学工具，可以可靠地定位和标记跨半球输入特定的大脑区域。结合记录神经元群的现代技术，这该方法有望开创以灵长类动物为中心的研究新时代，绘制大脑图谱需要结合两个半球的皮质活动以产生明确的电路感知并计划具体的行动。将大脑半球之间的神经元连接与其功能直接联系起来的能力视觉运动行为中的作用为研究长期存在的视觉运动行为提供了强大的工具假设一个半球特定运动向量的活动会抑制不同的运动向量另一方的运动活动。我们提出通过资本化来检验这一假设的实验关于眼球运动的特征明确、可精确测量和自然的本质他们的皮质由额叶眼场（FEF）控制。在我们的第一个具体目标中，我们将光学地识别并激活一个 FEF 中在记录时投射到半球的神经元来自另一个 FEF 中的受体神经元，以确定其中一个 FEF 中的活动是否增加半球降低了具有不同方向偏好的受体神经元的活动另一个半球。我们的第二个具体目标将使用类似的设置，但抑制跨半球皮质输入，以更彻底地测试控制的网络架构半球间的通讯。总的来说，拟议的实验将：1）识别皮质自然视觉和眼球运动过程中的跨半球协调机制为未来大脑半球间皮质通讯的工作做准备； 2）建立一个精确的、用于识别皮质输入的可靠工具，可大大改善皮质电路的映射。