SFB 1080: Molecular and Cellular Mechanisms of Neural Homeostasis

神经稳态指的是神经系统最显著的特征之一：它有能力在不断变化的环境中保持平衡和稳定的内部状态。这种持续的适应是由在分子、细胞和电路水平上起作用的稳态反馈机制来保证的，以维持神经系统在灵活设定值周围的功能。脑内稳态是指通过调节神经元功能，使神经元保持在一个支持信息传递和处理的最佳运行状态，以防止损伤或低效状态。因此，内稳态适应对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，我们探讨了神经系统在生理条件下维持其网络组件的功能、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，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、核糖停滞和蛋白质停滞以及突触前和突触后侧（A区和B区）的神经元形态和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，我们现在正在使用实验和计算方法加强对生理和改变条件下电路水平网络功能调节的研究（领域C）。在所有领域，我们也在探索微环境对神经元内稳态的影响，包括非神经元细胞（胶质细胞、内皮细胞和血管周围细胞），它们是调节内稳态机制的新出现的关键角色。利用不同的实验和计算方法的优势，我们的许多项目都试图对与内稳态机制相关的形态学、细胞和生化过程进行详细分析，并阐明构成神经系统内稳态的事件链。

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.