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

哺乳动物大脑中通过皮质巨突触进行皮质-皮质下通讯的神经元机制。

• 批准号: 383066895
• 负责人: Professor Dr. Alexander Groh, Ph.D.
• 金额: --
• 依托单位: Institut für Physiologie und Pathophysiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/383066895?language=en
• 关键词: Neuronal; mechanisms; cortico; subcortical; communication

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.

在过去的几十年里，对哺乳动物大脑皮层的研究大大提高了我们对大脑功能中皮层网络的认识。大脑皮层被认为是大脑的认知总部，容纳特定的皮层回路，用于决策，有意识的感知和行为协调。但是皮层是如何与大脑的其他部分进行交流来实现这些功能的呢？为了对感觉环境做出适当的反应，皮层必须委托给直接控制行为的神经系统的皮层下区域。皮质通过皮质输出通路调节不同的皮质下目标区域如丘脑、基底神经节和脑干的活动来协调对环境的反应。虽然皮质-皮质下信号传导对于大脑与环境之间的相互作用至关重要，但我们只是开始用现代解剖学和功能技术研究皮质-皮质下机制的神经元基础。拟议的项目调查的结构和功能机制之间的相互作用的皮质和皮质下的目标网络，通过利用在体内脑深部电生理学，光遗传学和细胞类型的特定方法在小鼠模型系统的组合。我们将首先绘制躯体感觉皮层的皮层下目标，并以细胞类型特异性方式表征这些连接的结构组织。基于这一解剖图，我们将在体外表征这些连接的突触生理学，随后在体内研究感觉处理和行为过程中皮质和单个靶核之间的信号传导。这个项目的重点是通过第5层锥体神经元的皮质输出，因为这些神经元将皮质与许多具有假定的巨大突触的皮质下靶核连接起来。巨大的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层皮层与上级丘（一个控制运动的前运动中心）以及前顶盖（通过强烈抑制来控制丘脑中的感觉信息）的相互作用。虽然这两个皮质靶向网络将是我们的起点，但长期目标是全面表征皮质-皮质下相互作用，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对感觉信号转化为行为的过程的机械理解。