Peptidergic Modulation of GABA Neurons in the Dorsal Vagal Complex

该项目的目的是促进对脑干中一组特定神经细胞（称为抑制性中间神经元）活动的理解，这些神经细胞负责控制大多数器官系统（如心脏、呼吸、消化系统）的功能。尽管它们在脑功能中的重要性是显而易见的，但抑制性中间神经元一直难以研究，因为它们与附近的其他神经细胞相似；人们对它们是如何被监管的知之甚少。一种基因修饰的“转基因”小鼠已经被开发出来，其中抑制中间神经元在紫外线下发出荧光。这些转基因小鼠将被用于与大脑其他部分相对隔离的抑制性中间神经元的研究，并将它们与附近其他类型的细胞分离开来。被研究的脑干区域接收来自大多数器官系统的输入，这些抑制性中间神经元在处理感觉信息方面起着关键作用，在向控制器官功能的神经细胞发送命令信号之前，帮助将其与来自大脑其他部分的信息整合起来。大脑中产生的最丰富的化学物质是一类阿片肽（即大脑的天然吗啡）。这些肽对器官功能有深远的影响，但对脑干中抑制性中间神经元的具体影响尚不清楚。本研究的部分目的是确定一类阿片肽对参与控制消化的抑制性中间神经元的特定活性的影响。这项研究更广泛的影响包括促进我们对这一重要大脑区域的理解，以及对研究生和本科生的科学训练。这些研究的结果将影响几个科学领域的研究，包括生理学、内分泌学、消化学和心血管生物学。结果将通过公布数据和在国家会议和专题讨论会上介绍来传播。

The aims of this project are to advance understanding about the activity of a specific set of nerve cells, called inhibitory interneurons, in the brain stem that are responsible for controlling the functions of most organ systems (e.g., cardiac, respiratory, digestive systems). Although their importance in brain function is evident, inhibitory interneurons have been difficult to study because they resemble other nearby nerve cells; little is known about how they are regulated. A strain of genetically modified "transgenic" mice has been developed, in which inhibitory interneurons fluoresce under ultraviolet light. These transgenic mice will be utilized to target the inhibitory interneurons for study in relative isolation from the rest of the brain and to separate them from other types of nearby cells. The area of the brain stem to be studied receives input from most organ systems, and these inhibitory interneurons play critical roles in processing that sensory information, helping to integrate it with information from the rest of the brain before sending command signals to the nerve cells that control organ function. Some of the most abundant chemicals made in the brain are a class of opioid peptides (i.e., the brain's natural morphine). These peptides have profound effects on organ function, but the specific effects on inhibitory interneurons in the brain stem are unknown. Part of this study aims to determine the effects of one class of these opioid peptides on the specific activities of inhibitory interneurons involved in controlling digestion. The broader impacts of the research include advancing our understanding of this important brain region and scientific training for both graduate and undergraduate students. Results of these studies will impact several scientific fields of study, including physiology, endocrinology, digestion, and cardiovascular biology. Results will be disseminated by publishing the data and by presentation at national meetings and symposia.