Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, 98101, USA.
Department of Physiology and Biophysics, University of Washington, Seattle, WA, 98195, USA.
Nat Commun. 2023 Aug 31;14(1):5300. doi: 10.1038/s41467-023-40812-x.
Sighs prevent the collapse of alveoli in the lungs, initiate arousal under hypoxic conditions, and are an expression of sadness and relief. Sighs are periodically superimposed on normal breaths, known as eupnea. Implicated in the generation of these rhythmic behaviors is the preBötzinger complex (preBötC). Our experimental evidence suggests that purinergic signaling is necessary to generate spontaneous and hypoxia-induced sighs in a mouse model. Our results demonstrate that driving calcium increases in astrocytes through pharmacological methods robustly increases sigh, but not eupnea, frequency. Calcium imaging of preBötC slices corroborates this finding with an increase in astrocytic calcium upon application of sigh modulators, increasing intracellular calcium through g-protein signaling. Moreover, photo-activation of preBötC astrocytes is sufficient to elicit sigh activity, and this response is blocked with purinergic antagonists. We conclude that sighs are modulated through neuron-glia coupling in the preBötC network, where the distinct modulatory responses of neurons and glia allow for both rhythms to be independently regulated.
叹气可防止肺泡在肺部塌陷，在缺氧条件下引发觉醒，并且是悲伤和宽慰的表现。叹气周期性地叠加在正常呼吸上，称为平稳呼吸。生成这些节律性行为的涉及到 preBötzinger 复合体（preBötC）。我们的实验证据表明，嘌呤能信号在小鼠模型中产生自发性和缺氧诱导的叹气是必需的。我们的结果表明，通过药理学方法驱动星形胶质细胞中的钙增加，可显著增加叹气频率，但不增加平稳呼吸频率。preBötC 切片的钙成像证实了这一发现，叹气调节剂的应用可增加星形胶质细胞中的钙，通过 G 蛋白信号增加细胞内钙。此外，preBötC 星形胶质细胞的光激活足以引起叹气活动，并且该反应可被嘌呤能拮抗剂阻断。我们得出结论，叹气是通过 preBötC 网络中的神经元-胶质细胞偶联来调节的，其中神经元和胶质细胞的不同调节反应允许两种节律独立调节。
