心と身体の制御に関わる「脳幹の孤束核」を読み解く〜脳の深くにある孤束核を低侵襲に観察する生体脳イメージング法を開発〜

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2025-04-05 生理学研究所

自然科学研究機構・生理学研究所の研究チームは、脳幹の孤束核を生体内で高解像度かつ低侵襲に観察する新技術「D-PSCAN法」を開発しました。この手法は、直角マイクロプリズムを組み合わせた「ダブルプリズム」を用い、小脳を損なうことなく孤束核の神経活動を可視化するものです。生体マウスを用いた実験では、迷走神経刺激に対する孤束核の反応を詳細に捉え、刺激強度に応じた閾値や感度増大、抑制効果などの複雑な応答特性が明らかになりました。また、腸管ホルモン投与による孤束核の活動変化も観察され、心と身体の相互作用の理解が進むと期待されます。この成果は、てんかんや難治性うつの治療法である迷走神経刺激療法の最適化や、食事・代謝・腸内環境など多方面の研究応用が見込まれます。研究成果は、2025年4月5日付でCell Reports Methods誌に掲載されました。

<関連情報>

細胞レベルの解像度で脳幹を低侵襲かつ広視野の2光子イメージング Minimally invasive, wide-field two-photon imaging of the brainstem at cellular resolution

Masakazu Agetsuma  ∙ Azumi Hatakeyama ∙ Daisuke Yamada ∙ … ∙ Akiyoshi Saitoh ∙ Junichi Nabekura ∙ Masayuki Sekiguchi
Cell Report Methods  Published;April 4, 2025
DOI:https://doi.org/10.1016/j.crmeth.2025.101010

Graphical abstract

心と身体の制御に関わる「脳幹の孤束核」を読み解く〜脳の深くにある孤束核を低侵襲に観察する生体脳イメージング法を開発〜

Motivation

The nucleus tractus solitarii (NTS), a brainstem structure, is proposed as a critical gateway for regulating emotions through brain-viscera communication and for therapies based on vagus nerve stimulation (VNS). However, how the NTS processes signals from various organs remains unclear. Investigating this has been challenging due to the NTS’s deep location beneath the cerebellum and its being surrounded by brainstem regions critical to vital functions, which makes direct observation difficult. To address this issue, we developed an in vivo two-photon imaging method using a double-prism-based optical interface, allowing minimally invasive observation while keeping the surrounding regions mostly intact.

Highlights

  • D-PSCAN is an in vivo brainstem imaging method that uses a double-prism optical interface
  • D-PSCAN enables low-invasive, wide-field brainstem imaging with cellular resolution
  • D-PSCAN detects neural responses specifically in the nucleus tractus solitarii (NTS)
  • D-PSCAN effectively characterizes NTS neuronal responses to vagus nerve stimulation

Summary

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.

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