Stimulation-Evoked Ca2+ Signals in Astrocytic Processes at Hippocampal CA3-CA1 Synapses of Adult Mice Are Modulated by Glutamate and ATP
Stimulation-Evoked Ca2+ Signals in Astrocytic Processes at Hippocampal CA3-CA1 Synapses of Adult Mice Are Modulated by Glutamate and ATP
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DOI：
10.1523/jneurosci.3319-14.2015
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发表时间：
2015-02-18
影响因子：
5.3
通讯作者：
Nagelhus, Erlend A.
中科院分区：
文献类型：
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作者：
Tang, Wannan;Szokol, Karolina;Nagelhus, Erlend A.
到目前为止，还很难揭示发生在成熟动物的精细星形细胞突起内的生理性钙事件。本研究的目的是探索神经元活动是否在成年小鼠的谷氨酸能突触上引起星形细胞钙信号。我们从成年小鼠的急性海马片上刺激了Schaffer侧支/连合纤维，转导了由胶质纤维酸性蛋白启动子驱动的遗传编码的钙指示剂GCaMP5E。双光子成像显示刺激诱发的星形细胞钙信号在细突和胞体中具有明显的潜伏期、上升速率和幅度。具体地说，这些过程中的钙信号比体细胞中的信号更快，幅度更大。P2嘌呤能和第I/II组代谢性谷氨酸受体(MGluR)拮抗剂联合使用可使两个星形细胞隔区的钙瞬变幅度降低30%-40%。单独阻断mGluRs只能适度地降低刺激诱发的钙信号的大小，而不能影响体细胞的钙反应。局部应用I组或I/II组mGluR激动剂或三磷酸腺苷(ATP)可产生模拟刺激引起的星形细胞钙反应的整体星形细胞钙信号。我们的结论是，成年小鼠CA3-CA1突触的刺激诱发的钙信号(1)不同于星形细胞胞体，(2)受谷氨酸和三磷酸腺苷的调节。
To date, it has been difficult to reveal physiological Ca2+ events occurring within the fine astrocytic processes of mature animals. The objective of the study was to explore whether neuronal activity evokes astrocytic Ca2+ signals at glutamatergic synapses of adult mice. We stimulated the Schaffer collateral/commissural fibers in acute hippocampal slices from adult mice transduced with the genetically encoded Ca2+ indicator GCaMP5E driven by the glial fibrillary acidic protein promoter. Two-photon imaging revealed global stimulation-evoked astrocytic Ca2+ signals with distinct latencies, rise rates, and amplitudes in fine processes and somata. Specifically, the Ca2+ signals in the processes were faster and of higher amplitude than those in the somata. A combination of P2 purinergic and group I/II metabotropic glutamate receptor (mGluR) antagonists reduced the amplitude of the Ca2+ transients by 30-40% in both astrocytic compartments. Blockage of the mGluRs alone only modestly reduced the magnitude of the stimulation-evoked Ca2+ signals in processes and failed to affect the somatic Ca2+ response. Local application of group I or I/II mGluR agonists or adenosine triphosphate (ATP) elicited global astrocytic Ca2+ signals that mimicked the stimulation-evoked astrocytic Ca2+ responses. We conclude that stimulation-evoked Ca2+ signals in astrocytic processes at CA3-CA1 synapses of adult mice (1) differ from those in astrocytic somata and (2) are modulated by glutamate and ATP.