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

项目概要/摘要 注意力，或选择信息进行进一步处理的能力，对生存至关重要。当有能力 集中注意力被破坏，如注意力缺陷障碍或空间忽视， 生活是毁灭性的有几个大脑区域的损害或可识别的活动发生变化 与注意力障碍有关这些包括海马旁皮质，称为后嗅皮质 (POR)在啮齿类动物中，丘脑的枕核，有时也被称为外侧后核， 啮齿动物的大脑这些区域的破坏与神经精神疾病有关，包括 精神分裂症和抑郁症，以及注意力相关缺陷，包括注意力缺陷障碍， 帕金森氏症和阿尔茨海默氏症。解剖学工作证实枕和POR是 鲁棒的和非线性连接的。到目前为止，枕为POR提供了最强的皮层下输入， 而POR向枕尾内侧区提供的输入比其他任何新皮质区都多 结构虽然这两个区域是在注意力的背景下单独研究的， POR-枕回路在注意力方面尚未被研究。PI建议使用体内电生理学， 计算建模和光遗传学来研究POR枕的组织和功能 电路.目标1将包括同时记录来自POR的单个单元和局部场电位数据 和枕使用tetrode记录方法，而大鼠执行视觉空间注意任务。PI将 分析单个单元和场电位数据，以确定两个区域之间的相关性， 在θ（6-10 Hz）和快γ（65-100 Hz）频带中的潜在振荡。在目标2中，PI将 使用目标1中收集的数据拟合一个通用线性模型网络，该网络考虑了观察到的相关性 在视觉空间注意力任务上的活动和表现。这个模型将被用来探讨如何POR- 枕回路功能以及回路中断如何影响行为。在目标3中，PI将使用 对投射POR的枕神经元以及投射POR的枕神经元的光遗传学抑制， 以测试模型的预测和任务中POR枕回路的参与。除了 这些研究阐明了引起注意的神经回路，将提供有关大脑组织的新信息。 以及大脑中丘脑皮层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。

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.