Control of thalamic circuits by a higher-order cortical area

项目总结/摘要 这个项目将研究高级皮层区域如何调节丘脑活动， perception.几乎所有的感觉信息都要经过丘脑到达大脑皮层， 丘脑被认为是一个简单的中继器。然而，新皮层也提供了强大的预测， 丘脑，下行皮质丘脑（CT）轴突数量超过上行丘脑皮质（TC）轴突 大约10：1。仅解剖学就暗示丘脑的功能是复杂的，皮质可能发挥作用， 对丘脑产生实质性的影响，并通过这种影响来影响它自己的输入。 CT通信在癫痫、精神分裂症和注意力缺陷障碍等疾病中发挥作用。一 对CT功能的彻底理解仍然是难以捉摸的，大多数CT通路的研究都是在探索 单峰初级感觉区或前额叶皮层。在解剖学和生理学上， 回路已经出现，提出了一个问题：是否每个皮层区域都有类似的反馈模式， 丘脑？不同的CT通路如何与不同类型的行为相关？ 海马旁皮质（在啮齿动物中称为后嗅皮质，POR）是一个多模态关联区 也是海马体视觉信息的主要来源。POR与 丘脑枕核（在啮齿动物中也称为外侧后核）。POR和枕 两者都与调节视觉注意力的网络有关，但几乎没有什么是已知的。 从POR到枕CT通路的结构和功能。 这个建议的中心目标是确定从皮质区POR的自上而下的投射如何影响大脑皮层的活动。 丘脑枕核在细胞、突触和回路机制水平上的功能。目标1是一个 更深入地了解CT投影的解剖结构，包括它们在POR中的起源及其投影 枕和邻近抑制回路的模式。为此，我将利用病毒转导策略， 免疫组织化学和成像。目的2是表征神经元的内在和突触生理特性 使用体外全细胞记录、光遗传学和表达Cre的小鼠 以单元和层相关的方式将线定位到目标投影。目的3是探讨这一功能 通过记录POR和枕中的单个单位和局部场电位活动， 在视觉刺激和CT通路的光遗传学操纵期间。 申请人将接受一流的培训，从两个共同赞助商与互补的专业知识，在cortico- 丘脑和皮质海马回路，以及细胞神经生理学，解剖学， 系统和行为神经科学。申请人的研究将揭示新的细胞，电路和功能 高级皮层区对视觉丘脑的控制特点。

Project Summary/Abstract This project will investigate how a higher-order cortical area modulates thalamic activity to shape sensory perception. Almost all sensory information passes through the thalamus en route to the cortex, and traditionally the thalamus has been considered a simple relay. However, the neocortex also provides robust projections to the thalamus, with descending corticothalamic (CT) axons outnumbering ascending thalamocortical (TC) axons by about 10:1. The anatomy alone implies that thalamic functions are complex, and that the cortex likely exerts a substantial influence on the thalamus and, through this, on its own inputs. CT communication plays a role in conditions such as epilepsy, schizophrenia, and attention deficit disorders. A thorough understanding of CT function has remained elusive, and most studies of CT pathways have explored unimodal primary sensory areas or the prefrontal cortex. Similar motifs in the anatomy and physiology of these circuits have emerged, raising the questions: Does every cortical area have a similar pattern of feedback to the thalamus? How are diverse CT pathways relevant to vastly different types of behavior? The parahippocampal cortex (called the postrhinal cortex, POR, in rodents), is a polymodal association area and the principal source of visual information to the hippocampus. The POR is heavily interconnected with the pulvinar nucleus of the thalamus (also known as the lateral posterior nucleus in rodents). POR and pulvinar have both been implicated in networks mediating visual attention, yet almost nothing is known about the structure and function of CT pathways from POR to pulvinar. The central goal of this proposal is to determine how top-down projections from cortical area POR influence the functions of the thalamic pulvinar nucleus at the level of cellular, synaptic, and circuit mechanisms. Aim 1 is a deeper understanding of the anatomy of the CT projection, including their origins in POR and their projection patterns in pulvinar and neighboring inhibitory circuits. For this I will utilize viral transduction strategies, immunohistochemistry, and imaging. Aim 2 is to characterize the intrinsic and synaptic physiological properties of the POR-to-pulvinar pathway using in vitro whole-cell recordings, optogenetics, and Cre-expressing mouse lines to target projections in a cell- and layer-dependent fashion. Aim 3 is to explore the functions of this pathway in awake animals by recording single-unit and local field potential activity in the POR and pulvinar during visual stimulation and optogenetic manipulation of the CT pathway. The applicant will receive first-rate training from two Co-Sponsors with complementary expertise in cortico- thalamic and corticohippocampal circuits, and in a range of techniques for cellular neurophysiology, anatomy, systems, and behavioral neuroscience. The applicant’s research will reveal new cellular, circuit, and functional features of corticothalamic control exerted by higher-order cortical area on the visual thalamus.