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12-lipoxygenase modulates l-type calcium channel-dependent long term potentiation by regulating calcium influx through l-type calcium channels.

机译:12-脂氧合酶通过调节通过L型钙通道的钙流入来调节L型钙通道依赖性的长期增强作用。

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摘要

Hippocampal long-term potentiation (LTP) is generally believed to underlie learning and the consolidation of memories in the mammalian brain. At CA3-CA1 Schaffer collateral synapses one of two fundamental calcium channels must be recruited for the induction of LTP: the NMDA receptor or the L-type calcium channel (LTCC). Though more than twenty years have passed since the finding that NMDA receptors are required for the induction of rip at CA3-CA1 synapses there is little agreement as to the molecules that mediate and modulate LTP induction. This may be partly due to the failure to discriminate between NMDA-receptor dependent and LTCC-dependent forms of LTP, each of which appears to involve distinct signal transduction and modulatory mechanisms. A previous study from our laboratory demonstrated that 12-lipoxygenase (12LOX) mediates metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD), a form of LTCC-dependent plasticity present in neonates. I therefore tested the hypothesis that 12LOX is a general mediator of LTCC-dependent plasticity at CA3-CA1 synapses by measuring LTCC-dependent LTP in adult hippocampal slices from a 12LOX knockout mouse. Herein I describe that, in contrast to its role as a downstream mediator of LTCC-dependent plasticity in the neonate, 12LOX is a selective upstream modulator of adult LTCC-dependent LTP, an action exerted via its regulation of calcium influx through LTCCs.
机译:通常认为海马长期增强(LTP)是哺乳动物脑中学习和记忆巩固的基础。在CA3-CA1,沙弗附属突触必须募集两个基本的钙通道之一来诱导LTP:NMDA受体或L型钙通道(LTCC)。尽管自从发现在CA3-CA1突触中诱导rip需要NMDA受体以来已经过去了二十多年,但是关于介导和调节LTP诱导的分子却几乎没有共识。这可能部分是由于无法区分LTP的NMDA受体依赖性和LTCC依赖性形式,每种形式似乎都涉及不同的信号转导和调节机制。我们实验室的先前研究表明,12-脂氧合酶(12LOX)介导了代谢型谷氨酸受体依赖性长期抑郁症(mGluR-LTD),这是新生儿中LTCC依赖性可塑性的一种形式。因此,我通过测量来自12LOX基因敲除小鼠的成年海马切片中LTCC依赖性LTP来验证12LOX是CA3-CA1突触时LTCC依赖性可塑性的一般介体的假设。在本文中,我描述了与它在新生儿中作为LTCC依赖性可塑性的下游介质的作用相反,12LOX是成年LTCC依赖性LTP的选择性上游调节剂,其作用是通过其调节通过LTCC的钙流入而发挥的。

著录项

  • 作者

    DeCostanzo, Anthony Joseph.;

  • 作者单位

    Columbia University.;

  • 授予单位 Columbia University.;
  • 学科 Biology Neuroscience.; Health Sciences Pharmacology.; Biology Physiology.
  • 学位 Ph.D.
  • 年度 2008
  • 页码 131 p.
  • 总页数 131
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经科学;药理学;
  • 关键词

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