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: 10541649
• 负责人: Garrett Neske
• 金额: $ 2.14万
• 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 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10541649
• 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.

项目总结 正常的感觉知觉和运动控制依赖于不同个体之间的动态功能交互作用 大脑皮层的区域。这些相互作用的功能障碍会导致毁灭性的神经和 神经精神障碍。而大脑皮层之间的相互作用被认为主要是通过 皮质神经元之间的直接突触连接(即皮质直接连接)，丘脑可能 在这些互动中也起着至关重要的作用。丘脑是大多数感官信息的必经中继器 发送到大脑皮层，大脑皮层向丘脑发送大量反馈投射，调节感觉 吞吐量。丘脑高级核团中的中继细胞接受特别强的皮质-丘脑突触 来自大脑皮层第5层投射神经元的输入，以及这些相同的丘脑中继细胞也发出强烈的 丘脑皮质突触传入次级/高级皮质。因此，除了单突触外， 皮质连接，不同的皮质区域也可能通过更高级的丘脑进行双突触相互作用。 (“跨丘脑皮质通路”)。尽管有之前的解剖学演示，但功能作用 对跨丘脑皮质通路的研究仍然知之甚少。我的建议的主要目标是 研究高级视觉丘脑(外侧后核，LP)如何调节功能相互作用 清醒、行为正常的小鼠初级(V1)和次级(V2)视皮层之间的关系，以及如何直接皮质 在V2中，输入与跨丘脑皮质输入整合。这些调查将极大地 增强我们对丘脑对动态皮质相互作用的贡献的理解，并扩展我的培训 在实验和分析技术方面，我正在为一个独立的调查员职位做准备。我的研究 该方案包括三个具体目标：1)研究V1和V2之间的跨丘脑相互作用 取决于觉醒，2)确定V1和V2之间跨丘脑通路的活动如何形成 V2神经元的视觉反应，以及3)研究直接皮质的突触输入是如何 投射和跨丘脑皮质投射由V2神经元整合，以及 这两个投射在主动视觉引导行为过程中携带的信息。在K99阶段，在 杰西卡·卡丁博士的指导和我的咨询委员会(迈克尔·希格利博士和迈克尔·迈克尔博士)的支持 Crair)，我将精通几种技术，包括体内神经元的双光子钙成像 群体和轴突终末以及体内的光遗传操作。在R00阶段及以后，我的 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 监测从事任务的动物的神经元活动)，以研究不同物种之间的动态相互作用 视觉系统的皮质和丘脑通路，这些相互作用是如何发展的，以及这些 在正常和病理状态下，相互作用都是视觉行为的基础。