反対の神経ペプチドと神経伝達物質の信号の回路調整
Marta E Soden1, Joshua X Yee2, Larry S Zweifel3,4
1Department of Pharmacology, University of Washington, Seattle, WA, USA. msoden@uw.edu.
Nature
|June 28, 2023
まとめ
ニューロンは神経伝達物質と神経ペプチドを同時に放出するが,その作用は相反する. この研究は GABAとニューロテンシン信号が ドーパミンニューロン活動を制御し 行動を最適化する方法を明らかにしています
科学分野:
- 神経科学
- 分子生物学
- 遺伝学
背景:
- ニューロンは,高速な神経伝達物質と遅い神経ペプチドを別々の膀から同時に放出する.
- 同時に放出される物質からの対極信号 (刺激/阻害) が神経回路を制御するメカニズムは不明である.
- 以前の研究では,これらのシグナル伝達経路を細胞および回路特異的に分離するための方法がなかった.
研究 の 目的:
- 相互作用する神経伝達物質と神経ペプチドが 神経回路の出力を調整する方法を研究する.
- 神経伝達物質と神経ペプチド遺伝子を 脳領域の異なる細胞タイプで 同時に操作する方法を開発する.
主な方法:
- 異なるDNA再結合を用いた 遺伝に基づく解剖学的解離手順を開発した.
- 独立して神経伝達物質と神経ペプチド遺伝子を標的にするためにCRISPR- Cas9変異を生成した.
- 脳の2つの領域 (横部下垂体と腹部上垂体領域) の異なる細胞タイプで同時に操作された遺伝子です.
主要な成果:
- 横部下垂体ニューロンがニューロテンシン (刺激性) とGABA (抑制性) を共生成し,腹部テグメンタル領域のドーパミンニューロン活性化を調整することを示した.
- 局所的なGABAニューロンを阻害し,ドーパミンニューロンを無抑制する (急速なカルシウム上昇).
- ドーパミンニューロンに Ntsr1 を介してゆっくりとしたカルシウム信号を直接生成し,行動反応を高めます.
結論:
- 反対の信号を持つ神経伝達物質 (GABA) と神経ペプチド (neurotensin) は,神経出力を制御するためにはっきりと作用する.
- これらの信号は,異なる時間スケールで,異なるセルタイプを通じて回路機能を最適化します.
- 神経制御のための新しいメカニズムを示しています
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