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.

在过去的几十年中，对哺乳动物皮质的研究大大提高了我们对脑功能中皮质网络的了解。脑皮质被视为大脑的认知总部，可容纳特定的皮质回路，以进行决策，有意识的看法和行为协调。但是，皮质如何与大脑其他部门进行交流以实现这些功能？为了对感觉环境执行适当的反应，皮层必须委派给直接控制行为的神经系统的皮层区域。皮层通过调节丘脑，基底神经节和通过皮质输出途径等多种皮质下靶区域的活性来协调对环境的反应。尽管皮质 - 皮质信号传导对于大脑与环境之间的相互作用至关重要，但我们只在开始研究具有现代解剖和功能技术的皮质增生机制的神经元基础。拟议的项目通过利用体内深度深度电生理学，光遗传学和细胞类型特异性方法的组合来研究皮质和皮质下靶网络之间相互作用的结构和功能机制。我们将首先绘制体感皮层的皮层靶标，并以细胞类型的特定方式表征这些连接的结构组织。基于此解剖图，我们将在体外表征这些连接的突触生理，然后在感觉处理和行为过程中研究体内皮质和单个靶核之间的信号传导。该项目的特殊焦点将是第5层中的锥体神经元的皮质输出，因为这些神经元将皮质与许多带有假定的巨型突触的皮层靶核连接起来。巨型突触转移具有极高效率的神经元信号。 我们对5层皮质相互作用特别感兴趣。虽然这两个皮质目标网络将是我们的起点，但长期目标是皮质增生相互作用的全面表征，这也将与诸如慢性疼痛之类的脑疾病有关。该项目的结果将有助于对感觉信号转换为行为的过程的机械理解。