SFB 1080: Molecular and Cellular Mechanisms of Neural Homeostasis

SFB 1080：神经稳态的分子和细胞机制

• 批准号: 221828878
• 金额: --
• 依托单位: Goethe-Universität Frankfurt am Main
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/221828878?language=en
• 关键词: SFB; 1080; Molecular; Cellular; Mechanisms

Neural homeostasis refers to one of the most remarkable features of the nervous system: its ability to maintain a balanced and stable internal state in response to a constant flow of inputs from an ever-changing environment. This continuous adaptation is ensured by homeostatic feedback mechanisms acting at the molecular, cellular and circuit levels to maintain nervous system functions around flexible set-points. Brain homeostasis is proposed to prevent damaging or inefficient states by adjusting neuronal function and keeping neurons in an optimal operating regime supporting information transfer and processing across neuronal circuits. Homeostatic adaptation is thus critical for the stability of the nervous system, while simultaneously allowing for a certain degree of structural, functional and organizational flexibility as a platform for development and adaptation to new environments and experiences. In other words, homeostatic stability and flexibility can be considered as two complementary and mutually dependent design principles of the brain. In the CRC1080 we explore the fundamental processes enabling the nervous system to maintain the functionality, adaptability and flexibility of its network components during physiological conditions, and also how these mechanisms are altered in pathological situations. We are aware that numerous mechanisms operating on different scales are involved. Therefore, our approach includes projects that analyze the molecular mechanisms of circuit maintenance through the regulation of apoptosis, neurogenesis, ribostasis and proteostasis, as well as neuronal morphology and synaptic transmission from the pre- and postsynaptic side (Areas A and B). After its implementation in the second funding period, we are now strengthening the study of the regulation of network function at a circuit level in physiological and altered conditions using experimental and computational approaches (Area C). Across all areas, we are also exploring the influence of the microenvironment on neuronal homeostasis by including non-neuronal cells (glia, endothelial cells and perivascular cells), which are newly emerging key players in the modulation of homeostatic mechanisms. Draw on the strengths of different experimental and computational approaches many of our projects search to arrive at a detailed analysis of the morphological, cellular and biochemical processes associated with homeostatic mechanisms and to elucidate the chain of events that constitutes homeostasis in the nervous system.

神经内稳态是指神经系统最显著的特征之一：它能够保持平衡和稳定的内部状态，以响应来自不断变化的环境的恒定输入流。这种持续的适应是通过在分子、细胞和电路水平上起作用的稳态反馈机制来确保的，以在灵活的设定点周围维持神经系统功能。脑内稳态被提出来通过调节神经元功能并使神经元保持在支持跨神经元回路的信息传递和处理的最佳操作机制来防止损伤或低效状态。因此，稳态适应对于神经系统的稳定性至关重要，同时允许一定程度的结构，功能和组织灵活性作为发展和适应新环境和经验的平台。换句话说，内稳态稳定性和灵活性可以被认为是大脑的两个互补和相互依赖的设计原则。在CRC1080中，我们探索了使神经系统能够在生理条件下保持其网络组件的功能性，适应性和灵活性的基本过程，以及这些机制在病理情况下如何改变。我们知道，这涉及到在不同规模上运作的许多机制。因此，我们的方法包括通过调节细胞凋亡，神经发生，核糖抑制和蛋白抑制，以及神经元形态和突触前和突触后侧（A区和B区）的突触传递来分析电路维持的分子机制的项目。在第二个资助期实施后，我们现在正在加强研究在生理和改变条件下使用实验和计算方法在电路水平上调节网络功能（C区）。在所有领域中，我们还通过包括非神经元细胞（神经胶质细胞，内皮细胞和血管周围细胞）来探索微环境对神经元稳态的影响，这些细胞是调节稳态机制的新出现的关键参与者。利用不同的实验和计算方法的优势，我们的许多项目都在寻找与稳态机制相关的形态学，细胞和生化过程的详细分析，并阐明构成神经系统稳态的事件链。