Altered hippocampal short-term plasticity and associative memory in synaptotagmin IV (-/-) mice
Altered hippocampal short-term plasticity and associative memory in synaptotagmin IV (-/-) mice
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DOI：
10.1002/hipo.20013
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发表时间：
2004-01-01
期刊：
影响因子：
3.5
通讯作者：
Storm, DR
中科院分区：
文献类型：
--
作者：
Ferguson, GD;Wang, HB;Storm, DR
突触结合蛋白IV（Syt IV）是一种活性诱导型分泌囊泡蛋白，被认为是神经递质释放的抑制剂（利特尔顿等人，自然400：757-760，1999）。为了验证这一假设在哺乳动物中枢神经系统的神经元，我们测量场兴奋性突触后电位（fEPSP）在海马切片制备Syt IV（-/-）小鼠。在谢弗侧支突触中，神经传递的基本特性基本上是正常的。然而，两种形式的短时程可塑性，成对脉冲易化（PPF）和强直后增强（PTP），在CA 1区的Syt IV（-/-）切片显着增强。类似地，这些突触的长时程增强（LTP）的早期阶段也得到增强。与在齿状颗粒细胞中观察到的低水平Syt IV一致，Syt IV（-/-）切片中的苔藓纤维突触显示出很大程度上正常的PPF和LTP。此外，我们发现Syt IV（-/-）小鼠在联想被动回避记忆范式中存在缺陷，但在新物体识别范式中正常。Syt IV（-/-）脑的突触结构和连接性与野生型小鼠没有区别，如免疫组织化学分析所示。这些结果表明，Syt IV是海马CA 1区短期可塑性的突触前负调节因子，并且是某些（但不是所有）形式的海马依赖性记忆所必需的。(C)2004 Wiley-Liss，Inc.
Synaptotagmin IV (Syt IV) is an activity-inducible, secretory vesicle protein that is thought to function as an inhibitor of neurotransmitter release (Littleton et al. Nature 400:757-760, 1999). To test this hypothesis in neurons of the mammalian CNS, we measured field excitatory postsynaptic potentials (fEPSPs) in hippocampal slice preparations from Syt IV (-/-) mice. At Schaffer collateral synapses, the basal properties of neurotransmission are largely normal. However, two forms of short-term plasticity, paired-pulse facilitation (PPF) and post-tetanic potentiation (PTP), are significantly enhanced in area CA1 of Syt IV (-/-) slices. Similarly, the early stages of long-term potentiation (LTP) are also enhanced at these synapses. Consistent with the low levels of Syt IV observed in dentate granule cells, the mossy fiber synapses in Syt IV (-/-) slices display largely normal PPF and LTP. In addition, we find that Syt IV (-/-) mice have deficits in the associative passive avoidance memory paradigm, but are normal in the novel object recognition paradigm. The synaptic architecture and connectivity of Syt IV (-/-) brains is indistinguishable from wild-type mice as indicated by immunohistochemical analysis. These results suggest Syt IV is a presynaptic negative regulator of short-term plasticity in area CA1 of the hippocampus and is required for some, but not all, forms of hippocampus-dependent memory. (C) 2004 Wiley-Liss, Inc.