The functional role of GABA/glycinergic cotransmitting neurons in the respiratory network

GABA/甘氨酸能共传递神经元在呼吸网络中的功能作用

• 批准号: 449503339
• 负责人: Professor Dr. Swen Hülsmann
• 金额: --
• 依托单位: Klinik für Anästhesiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/449503339?language=en
• 关键词: functional; role; GABA; glycinergic; cotransmitting

Breathing requires a complex pattern of activity of neurons within the respiratory network in the ventrolateral medulla oblongata and precise timing of synaptic inhibition is an essential contributor to proper function of this network and some respiratory neurons release GABAergic and glycinergic neurons. GABA/glycine cotransmitting neurons (GGCN) are very common in the embryonic ventrolateral medulla but their number decreases during maturation. Many neurons that are GGCN around birth develop into glycinergic neurons but still a significant number remains cotransmitting. This project aims to reveal the functional relevance of GGCNs for the network function by addressing four specific questions: (1) What are the physiological properties of individual GGCN in the respiratory network? (2) How are GGCN integrated into the circuitry of the respiratory network? How does optogenetic activating of GGCN alters the different phases of the respiratory rhythm? (4) What are the physiological consequences of inactivation of GGCN? (5) Are GGCN relevant to adjust the breathing rhythm to environmental changes? To achieve this aim, the project can rely on novel transgenic mouse tools allowing identification of GGCNs and cell specific expression of optogenetic tools.

呼吸需要延髓腹外侧的呼吸网络内的神经元的复杂活动模式，并且突触抑制的精确定时是该网络的适当功能的重要贡献者，并且一些呼吸神经元释放GABA能和甘氨酸能神经元。GABA/甘氨酸共传递神经元（GGCN）在胚胎延髓腹外侧区非常常见，但其数量在成熟过程中减少。许多在出生时为GGCN的神经元发育成甘氨酸能神经元，但仍有相当数量的神经元保持共传递。本项目旨在通过解决四个具体问题来揭示GGCN与网络功能的功能相关性：（1）呼吸网络中个体GGCN的生理特性是什么？(2)GGCN如何整合到呼吸网络的电路中？GGCN的光遗传学激活如何改变呼吸节律的不同阶段？(4)GGCN失活的生理后果是什么？(5)GGCN是否与根据环境变化调整呼吸节律相关？为了实现这一目标，该项目可以依赖于新的转基因小鼠工具，允许鉴定GGCN和细胞特异性表达的光遗传学工具。