Neocortical Control of the Thalamus

丘脑的新皮质控制

• 批准号: 9389617
• 负责人: Barry W Connors
• 金额: $ 51.88万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9389617
• 关键词: Address; Anatomy; Animals; Axon; Back; Behavior; Behavioral; Brain; Bypass; Cell Nucleus; Cells; Cognition; Communication; Consensus; Detection; Disease; Epilepsy; Equilibrium; Esthesia; Frequencies; Functional disorder; Genetic; Goals; Human; In Vitro; Lead; Mental disorders; Methods; Movement; Mus; Neocortex; Neurons; Optics; Output; Pathway interactions; Pattern; Perception; Physiological; Research; Role; Schizophrenia; Sensory; Somatosensory Cortex; Source; Synapses; Synaptic plasticity; System; Testing; Thalamic Nuclei; Thalamic structure; Ursidae Family; awake; cognitive function; dynamic system; feeding; improved; in vivo; insight; knowledge base; motor control; neocortical; nervous system disorder; neural circuit; neuropsychiatric disorder; optogenetics; sensory input; somatosensory; tool; treatment strategy; virtual

Project Summary/Abstract This project will investigate how the neocortex controls sensory processing in the thalamus. The neocortex and thalamus together constitute the majority of the mammalian brain and are crucial for sensation, motor control, and cognitive function. Virtually all sensory information enters the neocortex by way of the thalamus. The neocortex also provides massive top-down input to the thalamus. “Corticothalamic” (CT) projections outnumber ascending “thalamocortical” projections 10:1. This suggests that the cortex has a strong influence on thalamic activity and, thereby, on its own sensory input. Indeed, altered thalamic-cortical communication has been associated with disorders such as epilepsy and schizophrenia. Despite its obvious importance, a thorough understanding of CT function has been elusive. It is generally assumed that the cortex influences thalamic throughput by modulating the excitability of thalamic relay cells. However, in previous studies the scale and even the sign of modulation have varied. The complexity of CT circuits has long been an impediment to understanding them, but powerful genetic and optical tools can now be utilized to drive major advances. The central goal of our proposal is to determine how top-down projections from the neocortex influence thalamic sensory processing at the level of cellular, synaptic, and circuit mechanisms. We address this goal in three aims by utilizing the widely studied and technically tractable somatosensory system of the mouse. Aim 1 will focus on the extensive layer 6 CT system. In awake animals performing a sensory detection task, we will test our hypothesis that the TC system bidirectionally controls thalamic sensory processing, and that the sign of control is dynamically determined by layer 6 cell spike rates, short-term synaptic plasticity, and behavioral state. Aim 2 will focus on the layer 5 CT system, which is structurally distinct. Layer 5 CT projections, unlike those of layer 6, bypass the inhibitory thalamic reticular nucleus and the primary thalamic relay nuclei and make strong driver-type synapses in higher-order thalamic nuclei. Using specific Cre-expressing mouse lines and optogenetics, we will test the prediction that the dynamic balance of thalamic excitation and inhibition caused by layer 5 CT circuitry is dramatically different from that of layer 6. We will also characterize how these two CT circuits interact to produce integrated effects. Aim 3 will examine how the CT cells are themselves controlled, focusing on effects of diverse thalamic inputs. We, and others, have shown that neurons in layers 5 and 6 are powerfully innervated by thalamus, and that distinct thalamic nuclei have unique cortical projections. Here we will test the hypothesis that feed-forward inputs from first-order and second-order thalamic nuclei exert powerful but complementary control over CT cells of layers 5 and 6. Our project will provide much-needed insight about how CT systems influence thalamic processing. Such information will be essential for understanding neurological disorders involving CT communication.

项目摘要/摘要 该项目将研究新皮层如何控制丘脑中的感觉处理。新皮层和 丘脑构成大部分哺乳动物大脑，对于感觉，运动控制， 和认知功能。实际上，所有感官信息都通过丘脑进入新皮层。这 NeoCortex还为丘脑提供了大量的自上而下输入。 “ Corticothalamic”（CT）投影超过 上升“丘脑皮质”项目10：1。这表明皮质对丘脑有很大影响 活动，从而在其自身的感觉输入中。确实，丘脑皮层交流发生了变化 与癫痫和精神分裂症等疾病有关。尽管它很重要，但彻底 对CT功能的理解是难以捉摸的。通常认为皮层会影响丘脑 通过调节丘脑继电器细胞的兴奋来吞吐。但是，在以前的研究中，规模和 甚至调制的迹象也有所不同。长期以来，CT圆的复杂性一直是 了解它们，但是现在可以利用强大的遗传和光学工具来推动重大进展。 我们建议的核心目标是确定新皮层影响的自上而下的预测如何 在细胞，突触和电路机制水平上进行丘脑感觉处理。我们解决这个目标 三个目的是使用鼠标的广泛研究和技术障碍的体感系统。目标1 将专注于广泛的第6层CT系统。在执行感官检测任务的清醒动物中，我们将 检验我们的假设，即TC系统双向控制丘脑感官处理，并且该符号 控制的控制率是第6层细胞尖峰速率，短期突触可塑性和行为的动态确定 状态。 AIM 2将集中在第5层CT系统上，该系统在结构上是不同的。第5层CT项目，与 第6层的那些，绕过抑制性丘脑网状核和主要的丘脑继电器核和 在高阶丘脑核中制作强大的驱动器型突触。使用表达特定Cre的鼠标线 和光遗传学，我们将测试丘脑兴奋和抑制的动态平衡的预测 由第5层CT电路引起的与第6层的电路截然不同。我们还将表征这些 两个CT圆相互作用以产生综合效应。 AIM 3将检查CT细胞本身如何 受控的，重点关注潜水员丘脑输入的影响。我们和其他人已经表明，层中的神经元5 和6由丘脑有力地支配，而独特的丘脑核具有独特的皮质项目。 在这里，我们将测试以下假设，即从一阶和二阶丘脑核中馈送进料输入 对5和6层的CT单元格发挥强大但完全控制。 我们的项目将提供有关CT系统如何影响丘脑处理的急需的见解。这样的 信息对于理解涉及CT沟通的神经系统疾病至关重要。