Role of calcium, glutamate neurotransmission, and nitric oxide in spreading acidification and depression in the cerebellar cortex
Role of calcium, glutamate neurotransmission, and nitric oxide in spreading acidification and depression in the cerebellar cortex
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DOI：
10.1523/jneurosci.21-24-09877.2001
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发表时间：
2001-12-15
影响因子：
5.3
通讯作者：
Ebner, TJ
中科院分区：
文献类型：
--
作者：
Chen, G;Dunbar, RL;Ebner, TJ
本研究探讨了最近报道的快速蔓延的酸化和短暂的抑郁症在体内小脑皮质的机制。在大鼠和小鼠小脑皮质表面刺激引起的扩散酸化，用pH敏感染料中性红染色，并使用落射荧光成像监测。诱发扩散酸化的可能性取决于刺激参数;更大的频率和/或更大的幅度更有效。虽然平行纤维的激活定义了扩散的几何形状，但单独激活它们是不够的，因为用低Ca 2+阻断突触传递可以防止扩散酸化。突触后兴奋性增加也是一个主要因素。AMPA或代谢型谷氨酸受体拮抗剂的应用降低了引起扩散酸化的可能性，但更强的刺激强度仍然有效。相反，灌流GABA受体拮抗剂降低了阈值，唤起蔓延酸化。阻断一氧化氮合酶（NOS）增加了扩散酸化的阈值，而一氧化氮供体降低了阈值。然而，在神经元型NOS缺陷小鼠（B6; 129 S-Nos 1（tm 1 plh））中可诱发扩散性酸化。AMPA和代谢型谷氨酸受体拮抗剂和NOS抑制剂的存在下，皮层兴奋性的抑郁症，伴随着扩散酸化发生。这些研究结果表明，扩展酸化是依赖于细胞外的Ca 2+和谷氨酸神经传递的AMPA和代谢型谷氨酸受体的贡献，并调制一氧化氮。因此，扩散性酸化涉及突触前和突触后机制。我们假设再生过程，即，一个非被动的过程，是有效的，它使用皮层结构来解释高速传播。
This study investigated the mechanisms underlying the recently reported fast spreading acidification and transient depression in the cerebellar cortex in vivo. Spreading acidification was evoked by surface stimulation in the rat and mouse cerebellar cortex stained with the pH-sensitive dye neutral red and monitored using epifluorescent imaging. The probability of evoking spreading acidification was dependent on stimulation parameters; greater frequency and/or greater amplitude were more effective. Although activation of the parallel fibers defined the geometry of the spread, their activation alone was not sufficient, because blocking synaptic transmission with low Ca2+ prevented spreading acidification. Increased postsynaptic excitability was also a major factor. Application of either AMPA or metabotropic glutamate receptor antagonists reduced the likelihood of evoking spreading acidification, but stronger stimulation intensities were still effective. Conversely, superfusion with GABA receptor antagonists decreased the threshold for evoking spreading acidification. Blocking nitric oxide synthase (NOS) increased the threshold for spreading acidification, and nitric oxide donors lowered the threshold. However, spreading acidification could be evoked in neuronal NOS-deficient mice (B6; 129S-Nos1(tm1plh)). The depression in cortical excitability that accompanies spreading acidification occurred in the presence of AMPA and metabotropic glutamate receptor antagonists and NOS inhibitors. These findings suggest that spreading acidification is dependent on extracellular Ca2+ and glutamate neurotransmission with a contribution from both AMPA and metabotropic glutamate receptors and is modulated by nitric oxide. Therefore, spreading acidification involves both presynaptic and postsynaptic mechanisms. We hypothesize that a regenerative process, i.e., a nonpassive process, is operative that uses the cortical architecture to account for the high speed of propagation.