Neocortical Control of the Thalamus

项目总结/摘要 这个项目将研究新皮层如何控制丘脑的感觉处理。新皮层和 丘脑共同构成哺乳动物大脑的大部分，并且对于感觉，运动控制， 和认知功能。几乎所有的感觉信息都是通过丘脑进入新皮层的。的 新皮层还向丘脑提供大量自上而下的输入。“皮质丘脑”（CT）投射超过 “丘脑皮质”上行投射10：1这表明大脑皮层对丘脑有很强的影响， 活动，因此，对自己的感官输入。事实上，丘脑-皮层通讯的改变 与癫痫和精神分裂症等疾病有关。尽管它的重要性显而易见， 对CT功能的理解一直是难以捉摸的。一般认为皮质影响丘脑 通过调节丘脑中继细胞的兴奋性来提高吞吐量。然而，在以前的研究中， 甚至调制的符号也发生了变化。CT电路的复杂性长期以来一直是 虽然我们无法理解它们，但现在可以利用强大的遗传和光学工具来推动重大进展。 我们建议的中心目标是确定来自新皮层的自上而下的投射如何影响 在细胞、突触和电路机制水平上的丘脑感觉处理。我们致力于实现这一目标， 三个目标，利用广泛研究和技术上易于处理的鼠标体感系统。要求1 将集中在广泛的第六层CT系统。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，信号 的控制是动态决定的第6层细胞尖峰率，短期突触可塑性，和行为 状态目标2将重点关注第5层CT系统，该系统在结构上是不同的。第5层CT投影，不像 第6层的神经元绕过抑制性丘脑网状核和初级丘脑中继核， 在高级丘脑核中形成强大的驱动型突触。使用特异性Cre表达小鼠系 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电路引起的电流密度与第6层的电流密度显著不同。我们还将描述这些 两个CT电路相互作用以产生集成效应。目标3将检查CT细胞本身是如何 控制，专注于不同的丘脑输入的影响。我们和其他人已经证明，第5层的神经元 和6是由丘脑有力地支配，并且不同的丘脑核具有独特的皮质投射。 在这里，我们将测试的假设，前馈输入从一级和二级丘脑核团 对第5层和第6层的CT细胞施加有力但互补的控制。 我们的项目将提供关于CT系统如何影响丘脑处理的急需的见解。等 这些信息对于理解涉及CT通信的神经系统疾病至关重要。

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.