Roles of higher-order visual thalamus in state-dependent corticocortical communication

高阶视觉丘脑在状态依赖性皮质通讯中的作用

• 批准号: 9806621
• 负责人: Garrett Neske
• 金额: $ 10.32万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9806621
• 关键词: Address; Advisory Committees; Affect; Anatomy; Animals; Architecture; Area; Arousal; Axon; Behavior; Behavioral; Biological Models; Brain Injuries; Calcium; Cells; Characteristics; Cognition; Communication; Dependence; Detection; Disease; Electrophysiology (science); Feedback; Foundations; Functional disorder; Future; Genetic; Goals; Image; Impairment; In Vitro; Investigation; Label; Laser Scanning Microscopy; Lateral; Lateral posterior nucleus of thalamus; Lead; Learning; Light; Link; Literature; Medial; Mediating; Monitor; Mus; Neocortex; Neurons; Output; Pathologic; Pathway interactions; Perception; Phase; Play; Population; Positioning Attribute; Preparation; Presynaptic Terminals; Property; Research; Research Personnel; Research Proposals; Role; Schizophrenia; Secondary to; Sensory; Shapes; Slice; Synapses; Synaptic Transmission; Techniques; Testing; Thalamic Nuclei; Thalamic structure; Training; Trauma; V2 neuron; Visual; Visual Cortex; Visual Pathways; Visual Perception; Visual system structure; Visuospatial; Work; awake; experimental study; extracellular; in vivo; insight; motor control; neglect; neocortical; nervous system disorder; neuropsychiatric disorder; novel; optogenetics; post-doctoral training; response; two-photon; visual processing; visual stimulus

PROJECT SUMMARY Normal sensory perception and motor control depend on dynamic functional interactions among different regions of the neocortex. Dysfunction in these interactions can lead to devastating neurological and neuropsychiatric disorders. While interactions among cortical areas are thought to be mediated primarily by direct synaptic connections between cortical neurons (i.e. direct corticocortical connections), the thalamus may also play a crucial role in these interactions. The thalamus is an obligatory relay for most sensory information sent to the cortex, and the cortex sends massive feedback projections to thalamus, modulating sensory throughput. Relay cells in higher-order thalamic nuclei receive especially strong corticothalamic synaptic inputs from projection neurons in cortical layer 5, and these same thalamic relay cells also send strong thalamocortical synaptic inputs to secondary/higher order cortex. Thus, in addition to monosynaptic corticocortical connections, distinct cortical areas might also interact disynaptically via higher-order thalamus (the “transthalamic corticocortical pathway”). Despite previous anatomical demonstrations, the functional role of the transthalamic corticocortical pathway remains poorly understood. The primary goal of my proposal is to investigate how higher-order visual thalamus (the lateral posterior nucleus, LP) mediates functional interactions between primary (V1) and secondary (V2) visual cortex in awake, behaving mice, and how direct corticocortical inputs are integrated with transthalamic corticocortical inputs in V2. These investigations will significantly enhance our understanding of the thalamic contribution to dynamic cortical interactions and expand my training in experimental and analytical techniques as I prepare for an independent investigator position. My research proposal consists of three specific aims: 1) To study how the transthalamic interactions between V1 and V2 depend on arousal, 2) To determine how activity in the transthalamic pathway between V1 and V2 shapes visual responses in V2 neurons, and 3) To investigate how synaptic inputs from direct corticocortical projections and transthalamic corticocortical projections are integrated by V2 neurons, and what types of information these two projections carry during active visually guided behavior. During the K99 phase, under the guidance of Dr. Jessica Cardin and the support of my advisory committee (Drs. Michael Higley and Michael Crair), I will become proficient in several techniques, including in vivo 2-photon calcium imaging of neuronal populations and axon terminals and in vivo optogenetic manipulations. During the R00 phase and beyond, my goal is to combine an array of techniques (from detailed study of synaptic transmission in vitro to large-scale monitoring of neuronal activity in task-engaged animals) to study the dynamic interactions between various cortical and thalamic pathways of the visual system, how these interactions develop, and how these interactions underlie visual behavior in both normal and pathological states.

项目概要 正常的感觉知觉和运动控制取决于不同器官之间的动态功能相互作用 这些相互作用中的新皮质区域的功能障碍可能会导致破坏性的神经系统和疾病。 虽然皮层区域之间的相互作用被认为主要是由神经精神疾病介导的。 皮质神经元之间的直接突触连接（即直接皮质皮质连接），丘脑可能 在这些相互作用中，丘脑也发挥着至关重要的作用。 发送到皮层，皮层向丘脑发送大量反馈投射，调节感觉 高阶丘脑核中的中继细胞接收特别强的皮质丘脑突触。 来自皮质层 5 的投射神经元的输入，这些相同的丘脑中继细胞也发送强 因此，除了单突触之外，丘脑皮质突触还对二级/高级皮层进行输入。 皮质皮质连接，不同的皮质区域也可能通过高阶丘脑进行非突触相互作用 （“经丘脑皮质通路”）尽管之前有解剖学论证，但其功能作用仍然存在。 对经丘脑皮质通路的了解仍知之甚少 我的建议的主要目标是 研究高阶视觉丘脑（外侧后核，LP）如何介导功能相互作用 清醒、行为小鼠的初级（V1）和次级（V2）视觉皮层之间的关系，以及皮质皮质的直接作用 输入与 V2 中的经丘脑皮质输入整合。 增强我们对丘脑对动态皮质相互作用的贡献的理解并扩大我的训练 在我为独立调查员职位做准备时，我学习了实验和分析技术。 该提案包含三个具体目标：1）研究 V1 和 V2 之间的跨丘脑相互作用如何 取决于唤醒，2) 确定 V1 和 V2 之间的经丘脑通路的活动如何形成 V2 神经元的视觉反应，以及 3) 研究直接皮质皮质的突触输入如何 投射和经丘脑皮质投射由 V2 神经元整合，以及哪些类型 在 K99 阶段，这两个投影在主动视觉引导行为期间携带的信息。 杰西卡·卡丹博士的指导和我的顾问委员会（迈克尔·希格利博士和迈克尔· Crair），我将精通多种技术，包括神经元的体内 2 光子钙成像 在 R00 阶段及之后，我的群体和轴突末端以及体内光遗传学操作。 目标是结合一系列技术（从体外突触传递的详细研究到大规模 监测参与任务的动物的神经活动）以研究各种之间的动态相互作用 视觉系统的皮质和丘脑通路，这些相互作用如何发展，以及这些相互作用如何 相互作用是正常和病理状态下视觉行为的基础。