BRIEF DENDRITIC CALCIUM SIGNALS INITIATE LONG-LASTING SYNAPTIC DEPRESSION IN CEREBELLAR PURKINJE-CELLS
BRIEF DENDRITIC CALCIUM SIGNALS INITIATE LONG-LASTING SYNAPTIC DEPRESSION IN CEREBELLAR PURKINJE-CELLS
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DOI：
10.1073/pnas.89.15.7051
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发表时间：
1992-08-01
影响因子：
11.1
通讯作者：
AUGUSTINE, GJ
中科院分区：
文献类型：
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作者：
KONNERTH, A;DREESSEN, J;AUGUSTINE, GJ
我们已经进行了实验，旨在测试的假设，即长期抑郁症（LTD）的兴奋性突触传递在小脑皮层是由突触后钙浓度的上升。这些实验结合了用薄片膜片钳技术进行的突触功效的测量，与单个小脑浦肯野细胞中细胞内Ca浓度（[Ca]i）的Fura-2测量。同时激活的攀爬纤维和平行纤维支配的单个浦肯野细胞引起LTD的平行纤维浦肯野细胞兴奋性突触的传输。这种LTD与浦肯野细胞中[Ca]i的大而短暂的升高相关，显然是由于浦肯野细胞树突中通过电压门控Ca通道的Ca进入。攀援纤维活动产生的[Ca]i的升高是LTD所必需的，因为Ca螯合剂bis的加入，（2-氨基苯氧基）乙烷-N，N，N ′，N ′-四乙酸酯（BAPTA）到浦肯野细胞内部阻断了LTD。此外，由与平行纤维激活结合递送的去极化脉冲产生的[Ca]i升高，诱导了突触活动的抑制，在时间进程和幅度上都与LTD非常相似。因此，[Ca]i的上升似乎足以启动LTD。从这些结果中，我们得出结论，LTD的平行纤维浦肯野细胞突触是由一个简短的，攀登纤维介导的突触后[Ca]i的上升，LTD是由其他的，更长的寿命的过程，由突触后[Ca]i的上升触发。
We have performed experiments designed to test the hypothesis that long-term depression (LTD) of excitatory synaptic transmission in the cerebellar cortex is caused by a rise in postsynaptic Ca concentration. These experiments combined measurements of synaptic efficacy, performed with the thin slice patch clamp technique, with fura-2 measurements of intracellular Ca concentration ([Ca]i) in single cerebellar Purkinje cells. Simultaneous activation of the climbing fiber and parallel fibers innervating single Purkinje cells caused a LTD of transmission of the parallel fiber-Purkinje cell excitatory synapse. This LTD was associated with large and transient rises in [Ca]i in the Purkinje cell and apparently was due to Ca entry through voltage-gated Ca channels in the Purkinje cell dendrites. The rise in [Ca]i produced by climbing fiber activity was necessary for LTD, because addition of the Ca chelator bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate (BAPTA) to the interior of the Purkinje cell blocked LTD. Further, elevation of [Ca]i, produced by depolarizing pulses delivered in conjunction with parallel fiber activation, induced a depression of synaptic activity that closely resembled LTD in both time course and magnitude. Thus, a rise in [Ca]i appears to be sufficient to initiate LTD. From these results, we conclude that LTD of the parallel fiber-Purkinje cell synapse is initiated by a brief, climbing fiber-mediated rise in postsynaptic [Ca]i and that LTD is maintained by other, longer-lived processes that are triggered by the rise in postsynaptic [Ca]i.