Peptidergic Modulation of GABA Neurons in the Dorsal Vagal Complex

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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.