Neuronal mechanisms of cortico-subcortical communication via cortical giant synapses in the mammalian brain.

在过去的几十年里，对哺乳动物皮质的研究极大地促进了我们对大脑功能中的皮质网络的了解。大脑皮层被视为大脑的认知总部，为决策、意识感知和行为协调提供特定的皮质回路。但是，大脑皮层如何与大脑的其他部分沟通来完成这些功能呢？为了对感觉环境做出适当的反应，大脑皮层必须委派给直接控制行为的神经系统的皮质下区域。皮层通过皮质输出通路调节不同皮质下靶区的活动，如丘脑、基底节和脑干，从而协调对环境的反应。虽然皮质-皮质下信号对于大脑和环境之间的相互作用是必不可少的，但我们仅仅是在开始用现代解剖学和功能学技术来研究皮质-皮质下机制的神经元基础。这项拟议的项目通过结合体内脑深部电生理学、光遗传学和小鼠模型系统中特定细胞类型的方法来研究皮层和皮质下靶点网络之间相互作用的结构和功能机制。我们将首先绘制躯体感觉皮质的皮质下目标图，并以细胞类型特定的方式表征这些连接的结构组织。基于这一解剖图谱，我们将在体外表征这些连接的突触生理学特征，并随后研究在体内皮层和单个靶核之间、在感觉加工和行为过程中的信号传递。这个项目的重点将是通过第5层的锥体神经元进行皮质输出，因为这些神经元通过假定的巨大突触将皮质与许多皮质下靶核连接起来。巨型突触以极高的效率传递神经元信号。我们特别感兴趣的是第5层皮质与上丘的相互作用，上丘是控制运动的运动前中心，以及顶盖前的前部，它通过强烈的抑制作用来控制丘脑的感觉信息。虽然这两个皮质靶点网络将是我们的起点，但长期目标是全面描述皮质-皮质下相互作用的特征，这也将与慢性疼痛等脑部疾病相关。该项目的结果将有助于从机械上理解感官信号转化为行为的潜在过程。

Research on the mammalian cortex over the past decades has substantially advanced our knowledge about cortical networks in brain function. The cerebral cortex is viewed as the cognitive headquarter of the brain, accommodating specific cortical circuits for decision making, conscious perception and coordination of behavior. But how does the cortex communicate with the rest of the brain to fulfill these functions? In order to execute appropriate responses to the sensory environment, the cortex must delegate to subcortical areas of the nervous system which directly control behavior. The cortex coordinates responses to the environment by modulating the activity of diverse subcortical target areas such as the thalamus, basal ganglia and brainstem via cortical output pathways. While cortico-subcortical signaling is essential for the interaction between the brain and the environment, we are only at the beginning to investigate the neuronal basis of cortico-subcortical mechanisms with modern anatomical and functional techniques. The proposed project investigates the structure and the functional mechanisms underlying the interplay between the cortex and subcortical target networks by leveraging a combination of in vivo deep-brain electrophysiology, optogenetics, and cell-type-specific approaches in the mouse model system. We will first map the subcortical targets of the somatosensory cortex and characterize the structural organization of these connections in a cell-type specific manner. Based on this anatomical map, we will characterize the synaptic physiology of these connections in vitro and subsequently study the signaling between the cortex and individual target nuclei in vivo, during sensory processing and behavior. The particular focus of this project will be the cortical output via pyramidal neurons in layer 5, as these neurons connect the cortex with numerous subcortical target nuclei with putative giant synapses. Giant synapses transfer neuronal signals with exceptionally high efficiency. We are specifically interested in layer 5 cortical interactions with the superior colliculus, a premotor center which controls movements, as well as the anterior pretectum, which putatively gates sensory information in the thalamus by strong inhibition. While these two cortical target networks will be our starting point, the long-term goal is the comprehensive characterization of cortico-subcortical interactions which will also be relevant for brain diseases such as chronic pain. The results of this project will contribute to a mechanistic understanding of the processes underlying the transformation of sensory signals into behavior.