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去甲肾上腺素应激信号对促肾上腺皮质激素释放激素神经元网络活动的调节。

Regulation of corticotropin-releasing hormone neuronal network activity by noradrenergic stress signals.

机构信息

Centre for Neuroendocrinology, Department of Physiology, School of Biomedical Sciences, University of Otago, Dunedin, Otago, New Zealand.

出版信息

J Physiol. 2022 Oct;600(19):4347-4359. doi: 10.1113/JP283328. Epub 2022 Sep 12.

DOI:10.1113/JP283328
PMID:36040213
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9825848/
Abstract

Noradrenaline is a neurotransmitter released in response to homeostatic challenge and activates the hypothalamic-pituitary-adrenal axis via stimulation of corticotropin-releasing hormone (CRH) neurons. Here we investigated the mechanism through which noradrenaline regulates activity within the CRH neuronal network. Using a combination of in vitro GCaMP6f Ca imaging and electrophysiology, we show that noradrenaline induces a robust increase in excitability in a proportion of CRH neurons with many neurons displaying a bursting mode of activity. Noradrenaline-induced activation required α -adrenoceptors and L-type voltage-gated Ca channels, but not GABA/glutamate synaptic transmission or sodium action potentials. Exposure of mice to elevated corticosterone levels was able to suppress noradrenaline-induced activation. These results provide further insight into the mechanisms by which noradrenaline regulates CRH neural network activity and hence stress responses. KEY POINTS: GCaMP6f Ca imaging and on-cell patch-clamp recordings reveal that corticotropin-releasing hormone neurons are activated by noradrenaline with many neurons displaying a bursting mode of activity. Noradrenaline-induced activation requires α -adrenoceptors. Noradrenaline-induced Ca elevations persist after blocking GABA , AMPA, NMDA receptors and voltage-gated Na channels. Noradrenaline-induced Ca elevations require L-type voltage-gated Ca channels. Corticosterone suppresses noradrenaline-induced excitation.

摘要

去甲肾上腺素是一种在稳态挑战时释放的神经递质，通过刺激促皮质素释放激素 (CRH) 神经元来激活下丘脑-垂体-肾上腺轴。在这里，我们研究了去甲肾上腺素调节 CRH 神经元网络内活动的机制。我们使用体外 GCaMP6f Ca 成像和电生理学的组合，表明去甲肾上腺素在一定比例的 CRH 神经元中引起兴奋性的强烈增加，许多神经元显示出爆发活动模式。去甲肾上腺素诱导的激活需要 α-肾上腺素受体和 L 型电压门控 Ca 通道，但不需要 GABA/谷氨酸突触传递或钠动作电位。将小鼠暴露于升高的皮质酮水平能够抑制去甲肾上腺素诱导的激活。这些结果提供了更多关于去甲肾上腺素调节 CRH 神经网络活动的机制的信息，从而调节应激反应。关键点：GCaMP6f Ca 成像和细胞膜片钳记录显示，促皮质素释放激素神经元被去甲肾上腺素激活，许多神经元显示出爆发活动模式。去甲肾上腺素诱导的激活需要 α-肾上腺素受体。在阻断 GABA、AMPA、NMDA 受体和电压门控 Na 通道后，去甲肾上腺素诱导的 Ca 升高仍然存在。去甲肾上腺素诱导的 Ca 升高需要 L 型电压门控 Ca 通道。皮质酮抑制去甲肾上腺素诱导的兴奋。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ad7/9825848/1ac8dfdf53e6/TJP-600-4347-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ad7/9825848/6fce11d520bc/TJP-600-4347-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ad7/9825848/458b2993f46d/TJP-600-4347-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ad7/9825848/42c19a965548/TJP-600-4347-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ad7/9825848/1ac8dfdf53e6/TJP-600-4347-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ad7/9825848/6fce11d520bc/TJP-600-4347-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ad7/9825848/458b2993f46d/TJP-600-4347-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ad7/9825848/07fe07e3d6e9/TJP-600-4347-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ad7/9825848/42c19a965548/TJP-600-4347-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ad7/9825848/1ac8dfdf53e6/TJP-600-4347-g006.jpg

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