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

基本信息

  • 批准号:
    10892334
  • 负责人:
  • 金额:
    $ 20.35万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-09-30 至 2026-06-30
  • 项目状态:
    未结题

项目摘要

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.
项目摘要 正常的感觉知觉和运动控制取决于不同的动态功能相互作用 新皮层的区域。这些相互作用的功能障碍会导致毁灭性的神经系统和 神经精神疾病。尽管皮质区域之间的相互作用被认为是由 皮质神经元之间的直接突触连接(即直接皮层连接),丘脑可能 在这些相互作用中也起着至关重要的作用。丘脑是大多数感官信息的强制性继电器 发送到皮层,皮层将大量反馈项目发送给丘脑,调节感官 吞吐量。高阶丘脑核中的中继细胞接受特别强的皮质丘脑突触 皮质层5的投影神经元的输入,这些相同的丘脑继电器也会发出强烈 丘脑皮质突触输入到次级/高阶皮层。除了单突触 皮质皮质连接,不同的皮质区域也可能通过高阶丘脑脱节 (“经脑丘脑皮质皮层途径”)。尽管以前的解剖学演示,功能性作用 脑丘脑皮质皮质途径的理解仍然很少。我建议的主要目标是 研究高阶视觉丘脑(侧后核,LP)如何介导功能相互作用 在醒着的小鼠中,主要(v1)和次级(V2)视觉皮层之间,以及如何直接皮质皮层 输入与V2中的丘脑丘脑皮质皮质输入集成在一起。这些调查将大大 增强我们对丘脑对动态皮质相互作用的贡献的理解,并扩大我的培训 在为独立研究者的位置做准备时,在实验和分析技术中。我的研究 提案包括三个具体目的:1)研究V1和V2之间的脑丘脑相互作用如何 取决于唤醒,2)确定V1和V2形状之间的脑丘脑途径中的活性 V2神经元中的视觉反应,以及3)研究直接皮质皮质的合成输入如何 预测和脑丘脑皮质皮质项目由V2神经元整合,哪些类型的 信息在主动视觉指导行为期间随身携带的信息。在K99阶段, 杰西卡·卡丁(Jessica Cardin)博士的指导和我的咨询委员会的支持(迈克尔·希格利(Michael Higley)和迈克尔(Michael)博士 crair),我将精通多种技术,包括神经元的体内2-光子钙成像 种群和轴突末端以及体内光遗传操作。在R00阶段及以后,我 目标是结合一系列技术(从体外突触传播的详细研究到大规模 监测任务参与动物中的神经元活动)研究各种的动态相互作用 视觉系统的皮质和丘脑途径,这些相互作用如何发展以及如何 在正常状态和病理状态下的视觉行为是相互作用。

项目成果

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Garrett Neske其他文献

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{{ truncateString('Garrett Neske', 18)}}的其他基金

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
  • 财政年份:
    2019
  • 资助金额:
    $ 20.35万
  • 项目类别:
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
  • 财政年份:
    2019
  • 资助金额:
    $ 20.35万
  • 项目类别:

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