Agetsuma Masakazu, Hatakeyama Azumi, Yamada Daisuke, Kuniishi Hiroshi, Ito Chihiro, Takeuchi Eri, Tsuji Shinji, Tsutsumi Motosuke, Ichiki Takako, Otomo Kohei, Yoshioka Toshinori, Kobayashi Tomoko, Noritake Atsushi, Aoki Yoshitsugu, Nemoto Tomomi, Yukawa Hiroshi, Saitoh Akiyoshi, Nabekura Junichi, Sekiguchi Masayuki
Division of Homeostatic Development, National Institute for Physiological Sciences, Okazaki 444-8585, Japan; Institute for Quantum Life Science, National Institutes for Quantum Science and Technology (QST), Chiba 263-8555, Japan; Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510, Japan.
Institute for Quantum Life Science, National Institutes for Quantum Science and Technology (QST), Chiba 263-8555, Japan; Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510, Japan.
Cell Rep Methods. 2025 Apr 21;5(4):101010. doi: 10.1016/j.crmeth.2025.101010. Epub 2025 Apr 4.
Brain-viscera communication is crucial for 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 emotion regulation. 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 vivo, its underlying mechanisms remain unclear. Here, we developed a wide-field and deep-brain two-photon imaging method using a double-prism optical interface. This approach enables cellular-resolution imaging to specifically detect NTS neural activity while largely preserving the overlying cerebellum, a region also implicated in emotion regulation. We evaluated NTS neuronal responses to VNS and a gastrointestinal hormone, demonstrating the method's utility for investigating the vagus-NTS pathway in vivo.
脑-内脏通讯对于调节心理健康至关重要，迷走神经是介导这种相互作用的关键结构。临床上，人工迷走神经刺激（VNS）被用于治疗各种神经精神疾病，这凸显了迷走神经传入纤维在情绪调节中的重要性。孤束核（NTS）是一种脑干结构，被认为可接收来自迷走神经传入的信号，并将其传递至用于情绪调节的脑网络。然而，由于体内深层脑NTS区域的解剖结构复杂且难以进入，其潜在机制仍不清楚。在此，我们开发了一种使用双棱镜光学界面的广域和深层脑双光子成像方法。这种方法能够进行细胞分辨率成像，以特异性检测NTS神经活动，同时在很大程度上保留了也与情绪调节有关的覆盖小脑区域。我们评估了NTS神经元对VNS和一种胃肠激素的反应，证明了该方法在体内研究迷走神经-NTS通路的实用性。
