Control of thalamic circuits by a higher-order cortical area

项目摘要/摘要 这个项目将研究高阶皮质区域如何调节丘脑活动来塑造感觉。 感知力。几乎所有的感觉信息都是通过丘脑传递到大脑皮层的，而且传统上 丘脑一直被认为是一个简单的接力器。然而，大脑皮层也提供了强大的投射 丘脑，下降的皮质丘脑(CT)轴突数量多于上升的丘脑皮质(TC)轴突 大约10：1。解剖学本身就意味着丘脑的功能是复杂的，皮质可能会 对丘脑，并通过这一点，对其自身的输入产生重大影响。 CT交流在癫痫、精神分裂症和注意力缺陷障碍等疾病中发挥着作用。一个 对CT功能的彻底了解仍然难以捉摸，大多数关于CT途径的研究已经探索 单峰初级感觉区或前额叶皮质。在解剖学和生理学上有相似的主题 回路已经出现，引发了这样的问题：是否每个大脑皮层区域都有类似的反馈模式 丘脑？不同的CT路径与截然不同的行为类型有何关联？ 海马旁皮质(在啮齿动物中称为后皮质，POR)是一个多通道关联区。 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)。枕骨和枕骨 都与调节视觉注意的网络有关，但几乎对 枕叶至枕骨CT通路的结构与功能 这项建议的中心目标是确定从大脑皮层POR区域自上而下的投影如何影响 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 对CT投影的解剖有更深入的了解，包括它们在POR中的起源和它们的投影 枕骨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。目标2是描述固有的和突触的生理特性 用体外全细胞记录、光遗传学和表达Cre的小鼠研究POR到枕骨的通路 以依赖于单元格和层的方式将线指向目标投影。目标3是探索这一功能 通过记录POR和枕区的单单位和局部场电位活动在清醒动物中的通路 在视觉刺激和CT通路的光遗传操作期间。 申请者将接受两个共同赞助商的一流培训，这些共同赞助商具有互补的皮质专业知识- 丘脑和皮质-海马体回路，以及在细胞神经生理学、解剖学、 系统和行为神经科学。申请者的研究将揭示新的细胞、电路和功能 高阶皮质区域对视觉丘脑的控制特征。

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.