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内容記述 |
Brain-viscera communication plays a crucial role in regulating mental health, with the vagus nerve being a key structure mediating this interaction. Clinically, artificial vagus nerve stimulation (VNS) is used to treat various neuropsychiatric disorders, highlighting the importance of vagal afferent fibers in regulating emotion. The nucleus tractus solitarii (NTS) is a brainstem structure proposed to receive signals from vagal afferents and relay them to brain networks for emotion regulation. However, due to the anatomical complexity and difficulty in accessing the deep-brain NTS region in living animals, the mechanisms remain unclear. Here, we developed a wide-field and deep-brain two-photon imaging method using a double-prism based optical interface. This approach enables the identification of cellular-resolution neural activities in the NTS while preserving the cerebellum, which covers the NTS and is important for emotion regulation, mostly intact. Using this method, we systematically evaluated how NTS neurons respond to VNS. We observed differences and variations in the responsiveness of individual NTS neurons recorded simultaneously during VNS. We also detected changes in responsiveness to repeated VNS, with specific VNS conditions either enhancing or decreasing NTS neuronal responses. In addition, considering that emotional responses are influenced by various physiological stimuli and conditions, we evaluated our imaging system’s sensitivity to cholecystokinin-8 (CCK), a gastrointestinal hormone administered intravenously, as a more physiologically relevant stimulus than VNS. As a result, we observed immediate activation, as well as prolonged neural activation detected as continuous calcium transients. These results suggest that our method enables systematic evaluation of how NTS neurons respond to various stimuli, demonstrating its usefulness for investigating the role of the vagus-NTS pathway in vivo. |
