The inhibitory input to mouse cerebellar Purkinje cells is reciprocally modulated by Bergmann glial P2Y1 and AMPA receptor signaling
The inhibitory input to mouse cerebellar Purkinje cells is reciprocally modulated by Bergmann glial P2Y1 and AMPA receptor signaling
复制标题
小鼠小脑浦肯野细胞的抑制输入受到伯格曼胶质细胞 P2Y1 和 AMPA 受体信号传导的相互调节
作者：
Ramona Rudolph;H. M. Jahn;R. Courjaret;Nanette Messemer;F. Kirchhoff;J. Deitmer
突触传递已被证明是由神经胶质细胞的功能，但具体的神经胶质细胞的行动模式可能会有所不同，在不同的神经回路。我们已经使用野生型（WT）和胶质细胞特异性受体敲除小鼠的急性分离小脑切片测试了Bergmann GLIA（BG）是否参与塑造小鼠小脑皮质中的神经元通信的假设。ADP（100 µM）激活P2 Y1受体或AMPA（0.3 µM）激活谷氨酸能受体，可使浦肯野细胞中诱发抑制输入的强度分别增加80%和150%，且具有可逆性和可重复性。预先应用AMPA可抑制ADP诱导的反应，预先应用ADP可抑制AMPA诱导的反应。基因缺失或药理学阻断任一受体恢复了对另一受体激动剂的反应。ADP和AMPA反应均对虎红（可阻断囊泡谷氨酸摄取）和NMDA受体拮抗剂D-AP 5敏感。我们的研究结果提供了强有力的证据，即位于BG上的ADP和AMPA受体的激活导致谷氨酸的释放，这反过来又通过NMDA型谷氨酸受体激活抑制性中间神经元。这推断BG细胞通过其AMPA和P2 Y1受体相互抑制的代谢信号传导，将相互依赖地促进小脑皮质中浦肯野细胞活性的微调。GLIA 2016. GLIA 2016;64：1265-1280
Synaptic transmission has been shown to be modulated by glial functions, but the modes of specific glial action may vary in different neural circuits. We have tested the hypothesis, if Bergmann GLIA (BG) are involved in shaping neuronal communication in the mouse cerebellar cortex, using acutely isolated cerebellar slices of wild‐type (WT) and of glia‐specific receptor knockout mice. Activation of P2Y1 receptors by ADP (100 µM) or glutamatergic receptors by AMPA (0.3 µM) resulted in a robust, reversible and repeatable rise of evoked inhibitory input in Purkinje cells by 80% and 150%, respectively. The ADP‐induced response was suppressed by prior application of AMPA, and the AMPA‐induced response was suppressed by prior application of ADP. Genetic deletion or pharmacological blockade of either receptor restored the response to the other receptor agonist. Both ADP and AMPA responses were sensitive to Rose Bengal, which blocks vesicular glutamate uptake, and to the NMDA receptor antagonist D‐AP5. Our results provide strong evidence that activation of both ADP and AMPA receptors, located on BGs, results in the release of glutamate, which in turn activates inhibitory interneurons via NMDA‐type glutamate receptors. This infers that BG cells, by means of metabotropic signaling via their AMPA and P2Y1 receptors, which mutually suppress each other, would interdependently contribute to the fine‐tuning of Purkinje cell activity in the cerebellar cortex. GLIA 2016. GLIA 2016;64:1265–1280
DOI：
10.1007/s00424-014-1510-6
发表时间：
2014-04
期刊：
Pflügers Archiv - European Journal of Physiology
影响因子：
--
作者：
C. Lohr;A. Grosche;A. Reichenbach;Daniela Hirnet
通讯作者：
C. Lohr;A. Grosche;A. Reichenbach;Daniela Hirnet
DOI：
10.1073/pnas.97.15.8629
发表时间：
2000-07-18
影响因子：
11.1
作者：
Parpura, V;Haydon, PG
通讯作者：
Haydon, PG