Neocortical Control of the Thalamus

项目摘要/摘要 这个项目将研究新大脑皮层如何控制丘脑的感觉处理。新大脑皮层和 丘脑共同构成哺乳动物大脑的大部分，对感觉、运动控制、 和认知功能。几乎所有的感觉信息都通过丘脑进入大脑皮层。这个 新大脑皮层还为丘脑提供大量自上而下的输入。“皮质丘脑”(CT)投影量超过 上升的“丘脑皮质”投影为10：1。这表明皮质对丘脑有很强的影响。 活动，从而依靠它自己的感官输入。事实上，丘脑-大脑皮层通讯的改变 与癫痫和精神分裂症等疾病有关。尽管它显然很重要，但彻底的 对CT功能的了解一直难以捉摸。通常认为大脑皮质影响丘脑。 通过调节丘脑中继细胞的兴奋性来实现吞吐。然而，在以前的研究中，规模和 就连调制的符号也各不相同。CT电路的复杂性长期以来一直是阻碍 但强大的遗传和光学工具现在可以用来推动重大进步。 我们建议的中心目标是确定新大脑皮层自上而下的投影如何影响 丘脑在细胞、突触和回路机制水平上的感觉处理。我们在#年解决了这一目标 利用被广泛研究和技术上易于处理的小鼠体感系统达到三个目的。目标1 将重点放在广泛的第六层CT系统上。在清醒的动物执行感官检测任务时，我们将 测试我们的假设，即TC系统双向控制丘脑感觉处理，并且信号 由第6层细胞尖峰速率、短期突触可塑性和行为 州政府。目标2将重点介绍第五层CT系统，该系统在结构上是不同的。第5层CT投影，与 第6层，绕过抑制性丘脑网状核和初级丘脑中继核， 在高阶丘脑核团中制造强大的驱动型突触。使用表达Cre的特定小鼠系 和光遗传学，我们将检验丘脑兴奋和抑制动态平衡的预测 由第5层CT电路引起的与第6层的显著不同。我们还将描述这些 两个CT电路相互作用，产生综合效果。目标3将检查CT细胞本身是如何 受控，关注不同丘脑输入的影响。我们和其他人已经表明，第5层中的神经元 其中6个被丘脑强烈支配，不同的丘脑核团有独特的皮质投射。 在这里，我们将检验来自一阶和二阶丘脑核团的前馈输入 对第5层和第6层的CT细胞进行强大但互补的控制。 我们的项目将提供关于CT系统如何影响丘脑处理的迫切需要的见解。是这样的 信息对于了解涉及CT交流的神经疾病是必不可少的。

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.