Investigating the functional role of the pulvinar-postrhinal circuit in visuospatial attention

研究枕后-鼻后回路在视觉空间注意力中的功能作用

• 批准号: 10357892
• 负责人: Sean Gregory Trettel
• 金额: $ 7.17万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10357892
• 关键词: Address; Affect; Alzheimer' s Disease; Anatomy; Animal Behavior; Animals; Area; Attention; Attention Deficit Disorder; Attention deficit hyperactivity disorder; Behavior; Brain; Cell Nucleus; Cells; Cognition; Computer Models; Computing Methodologies; Cues; Data; Data Correlations; Disease; Electrophysiology (science); Frequencies; Functional disorder; Human; Impairment; Implant; Individual; Lateral posterior nucleus of thalamus; Lead; Linear Models; Location; Major Depressive Disorder; Mental Depression; Methods; Modeling; Neurons; Parkinson Disease; Pattern; Performance; Phase; Physiological; Play; Primates; Property; Pulvinar structure; Quality of life; Rattus; Research; Response to stimulus physiology; Rodent; Role; Schizophrenia; Sensory; Stimulus; Structure; Techniques; Testing; Thalamic structure; Time; Viral; Viral Vector; Visual; Visuospatial; Work; cell cortex; designer receptors exclusively activated by designer drugs; in vivo; mathematical model; multisensory; neocortical; nerve supply; network models; neuropsychiatry; optogenetics; predictive modeling; relating to nervous system; response; social anxiety; spatial neglect; success

Project Summary / Abstract Attention, or the ability to select information for further processing, is critical for survival. When the ability to focus attention is disrupted, such as in attention deficit disorder or spatial neglect, the decrease in quality of life can be devastating. There are several brain areas in which damage or identifiable activity changes correlate with attentional dysfunction. These include the parahippocampal cortex, called the postrhinal cortex (POR) in rodents, and the pulvinar nucleus of the thalamus, sometimes called the lateral posterior nucleus in the rodent brain. Disruption of these regions is implicated in neuropsychiatric conditions, including schizophrenia and depression, as well as attention-related deficits, including attention deficit disorder, Parkinson’s disease, and Alzheimer’s disease. Anatomical work confirms that the pulvinar and the POR are robustly and reciprocally connected. The pulvinar provides, by far, the strongest subcortical input to the POR, and the POR provides more input to the caudomedial region of the pulvinar than any other neocortical structure. Whereas these two regions have been studied individually in the context of attention, the role of the POR-pulvinar circuit in attention has not been investigated. The PI proposes to use in vivo electrophysiology, computational modeling, and optogenetics to investigate the organization and function of the POR-pulvinar circuit. Aim 1 will consist of simultaneously recording single unit and local field potential data from the POR and the pulvinar using tetrode recording methods while rats perform a visuospatial attention task. The PI will analyze both single unit and field potential data for correlations between the two regions with a focus on field potential oscillations in the theta (6-10 Hz) and fast gamma (65-100 Hz) frequency bands. In aim 2, the PI will use the data collected in Aim 1 to fit a General Linear Model network that accounts for observed correlated activity and performance on the visuospatial attention task. This model will be used to explore how the POR- pulvinar circuit functions and how disruptions in the circuit might affect behavior. In aim 3, the PI will use optogenetic inhibition of the POR-projecting pulvinar neurons, as well as the pulvinar-projecting POR neurons, to test the predictions of the model and the involvement of the POR-pulvinar circuit in the task. In addition to elucidating the circuits underlying attention, these studies will provide new information about the organization and function of thalamocortical and corticothalamic circuits in the brain. This research will inform future research aimed at understanding and treating attentional dysfunction.

项目摘要 /摘要 注意或选择信息进行进一步处理的能力对于生存至关重要。什么时候 专注注意力是残疾人的，例如注意力缺陷障碍或空间忽视，质量下降 生活可能是毁灭性的。有几个大脑区域会发生损害或可识别的活动变化 与注意力障碍相关。其中包括帕拉希波克胶皮层，称为骨皮皮质 （POR）在啮齿动物中，以及丘脑的pulvinar核，有时称为侧后核 啮齿动物的大脑。这些区域的破坏是在神经精神疾病中暗示的，包括 精神分裂症和抑郁症以及与注意力相关的缺陷，包括注意缺陷障碍， 帕金森氏病和阿尔茨海默氏病。解剖工作证实了pulvinar和por 牢固且相互连接。到目前 并且POR比其他任何新皮层提供了对脉泊纳尔的尾部区域的输入 结构。尽管这两个区域已在关注的背景下单独研究，但 尚未研究注意力的POR-PULVINAR电路。 PI使用体内电生理学的建议， 计算建模和光遗传学，以研究POR-PULVINAR的组织和功能 电路。 AIM 1将包括简单地记录单个单元和局部现场潜在数据 大鼠执行视觉注意任务时，使用四极管记录方法的pulvinar。 PI会 分析两个区域之间的相关性的单个单元和现场潜在数据，重点是 Theta（6-10 Hz）和快速伽玛（65-100 Hz）频带的潜在振荡。在AIM 2中，PI将 使用AIM 1中收集的数据拟合一个通用的线性模型网络，该网络对观察到的相关性相关 视觉注意任务的活动和表现。该模型将用于探索如何 Pulvinar电路的功能以及电路中的破坏可能影响行为。在AIM 3中，PI将使用 por射击脉冲神经元以及pulvinar-projecting por神经元的光遗传学抑制作用， 测试模型的预测以及por-pulvinar电路参与任务的预测。此外 阐明关注的电路，这些研究将提供有关组织的新信息 大脑中丘脑皮质和皮质丘脑回路的功能。这项研究将为未来提供信息 旨在理解和治疗注意力障碍的研究。