一个下丘脑电路用于对皮质激素分泌的昼夜调节
Oscar D Ramirez-Plascencia1,2, Roberto De Luca1,2, Natalia L S Machado1,2
1Department of Neurology, Division of Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Research square
|July 23, 2024
概括
背中侧下丘脑 (DMH) 通过两个途径调节每日皮质醇节律:谷氨酸刺激和GABAergic抑制关键的下丘脑神经元,这对于预测活性阶段至关重要.
科学领域:
- 神经科学是一个神经科学.
- 内分泌学 在内分泌学.
- 时间生物学 时间生物学
背景情况:
- 皮质醇分泌遵循日常节律,对活跃周期至关重要,并且在抑郁症中受到干扰.
- 上神经核 (SCN) 调节这种节奏,影响对心室内核 (PVH) 皮质otropin释放激素 (CRH) 神经元.
- 背中下丘脑 (DMH) 作为SCN和PVH之间的中间体,但其调节皮质醇节律的作用尚不清楚.
研究的目的:
- 研究DMH神经元在调节皮质 (Cort) 分泌的每日节律中的作用和突触机制.
- 阐明DMH通过哪些特定途径影响下丘脑-垂体-上腺 (HPA) 轴.
主要方法:
- 在动物中,切除和化学遗传/光遗传操纵DMH谷氨基基 (DMHVglut2) 和GABAergic (DMHVgat) 神经元.
- 在DMH中Vglut2的基因删除.
- 在下丘脑切片中进行电生理学记录,以评估突触传输.
- 评估Cort水平和昼夜节律.
主要成果:
- 消去或抑制DMHVglut2神经元将高峰Cort水平降低了40-70%,表明需要谷氨酸信号传递.
- 刺激DMHVglut2神经元增加了Cort水平,它们的激活直接激发了PVHCRH神经元.
- 扰乱DMHVgat神经元功能也减少了昼夜Cort峰值,刺激增加了Cort.
- DMHVgat神经元通过内部神经元抑制PVHCRH神经元,形成一种对Cort分泌至关重要的消毒途径.
结论:
- 两个平行的DMH通路 (谷氨基激发激发和GABAergic消毒抑制) 将时间信息传输到PVHCRH神经元.
- 这些路径共同协调Cort的每日激增,预期活动阶段.
- 这些发现澄清了调节Cort分泌的神经回路以及SCN,DMH和PVH之间的相互作用.
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