Brain activity regulates loose coupling between mitochondrial and cytosolic Ca2+ transients
Brain activity regulates loose coupling between mitochondrial and cytosolic Ca2+ transients
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大脑活动调节线粒体和胞质 Ca2 瞬变之间的松散耦合
DOI：
10.1038/s41467-019-13142-0
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发表时间：
2019-11-21
影响因子：
16.6
通讯作者：
Cheng, Heping
中科院分区：
文献类型：
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作者：
Lin, Yuan;Li, Lin-Lin;Cheng, Heping
线粒体钙([Ca2+]mito)动力学在调节包括生物能量学在内的基本细胞和细胞器功能中起着至关重要的作用。然而，活体内神经元[Ca~(2+)]有丝分裂的动力学及其受大脑活动的调节在很大程度上是未知的。通过在清醒行为小鼠的初级运动(M1)和视觉皮质(V1)中进行双光子钙成像，我们发现离散的[Ca~(2+)]有丝分裂瞬间通过体细胞和树突线粒体网络同步发生，并以概率而不是确定性的方式与胞浆钙([Ca~(++)]Cyto)瞬间结合。细胞内[Ca~(2+)]瞬变的幅度、持续时间和频率是耦合的重要决定因素，在跑步机运动(在M1神经元中)和视觉刺激(在V1神经元中)时，耦合保真度大大增加。此外，钙/钙调蛋白激酶II在机械上参与了这一动态偶联过程的调节。因此，活性依赖的动态[Ca~(2+)]-有丝分裂-[Ca~(2+)]细胞偶联为[Ca~(2+)]有丝分裂对脑活动的解码提供了一个重要的机制，从而调节线粒体生物能量学以满足神经元能量需求的波动以及神经元的信息处理。
Mitochondrial calcium ([Ca2+]mito) dynamics plays vital roles in regulating fundamental cellular and organellar functions including bioenergetics. However, neuronal [Ca2+]mito dynamics in vivo and its regulation by brain activity are largely unknown. By performing two-photon Ca2+ imaging in the primary motor (M1) and visual cortexes (V1) of awake behaving mice, we find that discrete [Ca2+]mito transients occur synchronously over somatic and dendritic mitochondrial network, and couple with cytosolic calcium ([Ca2+]cyto) transients in a probabilistic, rather than deterministic manner. The amplitude, duration, and frequency of [Ca2+]cyto transients constitute important determinants of the coupling, and the coupling fidelity is greatly increased during treadmill running (in M1 neurons) and visual stimulation (in V1 neurons). Moreover, Ca2+/calmodulin kinase II is mechanistically involved in modulating the dynamic coupling process. Thus, activity-dependent dynamic [Ca2+]mito-to-[Ca2+]cyto coupling affords an important mechanism whereby [Ca2+]mito decodes brain activity for the regulation of mitochondrial bioenergetics to meet fluctuating neuronal energy demands as well as for neuronal information processing.