Exocytosis of vesicular zinc reveals persistent depression of neurotransmitter release during metabotropic glutamate receptor long-term depression at the hippocampal CA3-CA1 synapse
Exocytosis of vesicular zinc reveals persistent depression of neurotransmitter release during metabotropic glutamate receptor long-term depression at the hippocampal CA3-CA1 synapse
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DOI：
10.1523/jneurosci.0475-06.2006
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发表时间：
2006-05-31
影响因子：
5.3
通讯作者：
Noebels, Jeffrey L.
中科院分区：
文献类型：
--
作者：
Jing Qian;Noebels, Jeffrey L.
胞吐作用可通过囊泡锌释放的荧光检测在哺乳动物脑切片中直接测量。低水平诱发锌信号[ Zn]（t）的检测首先在富含锌的海马苔藓纤维通路中得到证实，并且需要使用高频突触前刺激。在这里，我们表明，释放后，个人的动作电位可以可靠地检测到，即使在非苔藓纤维，锌贫突触在海马，时间分辨率的技术的一个主要增强。放射层中锌阳性CA 3-CA 1 Schaffer侧支/连合突触释放特性的短期促进与苔藓纤维处的突触不同，但与EPSP [场EPSP（fEPSP）]测量的结果相似。N型Ca 2+通道毒素ω-芋螺毒素GVIA同等地抑制[ Zn]（t）和fEPSP，并且由[ Zn]（t）揭示的神经肽Y、巴氯芬和腺苷对神经递质释放的调节与对fEPSP测量的调节非常相似。海马突触可塑性的一个长期存在的争议涉及这些突触的长期抑制（LTD）的网站。使用锌释放作为胞吐事件的直接标志物和谷氨酸释放的替代标志物，我们证明了突触前释放的持续抑制发生在DHPG [（S）-3，5-dihydroxyphenylglycine]诱导的LTD在该突触的晚期表达中。用锌荧光检测来检查释放动力学的能力将有助于探索许多CNS突触的胞吐作用的分子药理学和可塑性。
Exocytosis can be directly measured in mammalian brain slices by fluorescence detection of vesicular zinc release. Detection of the low-level evoked zinc signal [ Zn](t) was first demonstrated at the zinc-rich hippocampal mossy fiber pathway and required the use of high-frequency presynaptic stimulation. Here, we show that release after individual action potentials can be reliably detected even at non-mossy fiber, zinc-poor synapses in the hippocampus, a major enhancement in the temporal resolution of the technique. Short-term facilitation of release properties of zinc-positive CA3-CA1 Schaffer collateral/commissural synapses in the stratum radiatum differ from those at mossy fibers but are similar to those measured for the EPSP [ field EPSP ( fEPSP)]. The N-type Ca2+ channel toxin omega-conotoxin GVIA inhibited both the [ Zn](t) and fEPSP equally, and the modulation of neurotransmitter release by neuropeptide Y, baclofen, and adenosine as revealed by [ Zn](t) closely resembles that measured for the fEPSP. A long-standing controversy in hippocampal synaptic plasticity involves the site of long-term depression ( LTD) at these synapses. Using zinc release as a direct marker for exocytotic events and a surrogate marker for glutamate release, we demonstrate that persistent depression of presynaptic release occurs in the late expression of DHPG [( S)-3,5-dihydroxyphenylglycine]-induced LTD at this synapse. The ability to examine release dynamics with zinc fluorescence detection will facilitate exploration of the molecular pharmacology and plasticity of exocytosis at many CNS synapses.