Preinspiratory calcium rise in putative pre-Botzinger complex astrocytes
Preinspiratory calcium rise in putative pre-Botzinger complex astrocytes
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DOI：
10.1113/jphysiol.2012.231464
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发表时间：
2012-10-01
影响因子：
5.5
通讯作者：
Ikegaya, Yuji
中科院分区：
文献类型：
--
作者：
Okada, Yasumasa;Sasaki, Takuya;Ikegaya, Yuji
关键点自主呼吸节律是维持生命所必需的，它产生于低位脑干。延髓腹外侧区称为Pre-Botzinger Complex(Pre-Botzinger Complex)，是呼吸节律产生的核心。尽管之前广泛的研究集中在神经元上，但呼吸节律是如何产生的机制还没有完全被理解。在这里，我们证明了在吸气性神经元活动之前，前BotC中的非神经性胶质细胞(假定的星形胶质细胞的子集)被周期性地激活，在神经元活动被阻断期间，假定的星形胶质细胞的周期性活动持续，并且刺激前BotC中的星形胶质细胞诱导吸气性神经元放电。这些发现，加上先前的报告，即阻断星形胶质细胞的新陈代谢，取消吸气神经输出，表明星形胶质细胞在功能上参与了呼吸节律的产生。这些结果将有助于我们更好地理解呼吸节律是如何产生的，以及在各种病理条件下呼吸输出是如何被干扰的。摘要神经吸气活动起源于延髓腹外侧区，称为前Botzinger复合体(PreBotzinger Complex，Pre-Botzinger Complex)，但呼吸节律发生的机制尚不完全清楚。最近，不仅神经元，而且星形胶质细胞在中枢呼吸控制中的作用引起了相当大的关注。在这里，我们报告了我们的发现，在节律活跃的脑片中，假定星形胶质细胞的一部分细胞内钙升高先于吸气性神经元放电。成百上千个BotC前细胞的功能钙成像显示，部分星形胶质细胞在吸气前表现出节律性钙升高，延迟约2 S。这些吸气前星形胶质细胞即使在河豚毒素阻断神经元活动的情况下仍保持节律活动，节律频率降低，这些节律的细胞间时相分离。此外，对可能的星形胶质细胞的光遗传刺激诱导了吸气神经元的放电。这些发现提出了这样一种可能性，即前BotC区的星形胶质细胞积极参与节律活跃脑片的呼吸节律的产生。
Key points Autonomic respiratory rhythm is essential to maintain lives and is generated in the lower brainstem. The ventrolateral medullary region, called the pre-Botzinger complex (preBotC), is the kernel for respiratory rhythm generation. Despite previous extensive studies focusing on neurons, the mechanism of how respiratory rhythm is generated has not been fully understood. Here we show that non-neuronal glial cells (a subset of putative astrocytes) in the preBotC are periodically activated preceding inspiratory neuronal activity, periodic activity of putative astrocytes persists during blockade of neuronal activity, and stimulation of astrocytes in the preBotC induces inspiratory neuronal firings. These findings together with the previous report that blockade of astrocytic metabolism abolishes inspiratory neural output suggest that astrocytes are functionally involved in respiratory rhythm generation. These results will help us better understand how respiratory rhythm is generated and how respiratory output is disturbed in various pathological conditions. Abstract The neural inspiratory activity originates from a ventrolateral medullary region called the pre-Botzinger complex (preBotC), yet the mechanism underlying respiratory rhythmogenesis is not completely understood. Recently, the role of not only neurons but astrocytes in the central respiratory control has attracted considerable attention. Here we report our discovery that an intracellular calcium rise in a subset of putative astrocytes precedes inspiratory neuronal firing in rhythmically active slices. Functional calcium imaging from hundreds of preBotC cells revealed that a subset of putative astrocytes exhibited rhythmic calcium elevations preceding inspiratory neuronal activity with a time lag of approximately 2 s. These preinspiratory putative astrocytes maintained their rhythmic activities even during the blockade of neuronal activity with tetrodotoxin, whereas the rhythm frequency was lowered and the intercellular phases of these rhythms were decoupled. In addition, optogenetic stimulation of preBotC putative astrocytes induced firing of inspiratory neurons. These findings raise the possibility that astrocytes in the preBotC are actively involved in respiratory rhythm generation in rhythmically active slices.