mGluRs induce a long-term depression in the ventral tegmental area that involves a switch of the subunit composition of AMPA receptors
mGluRs induce a long-term depression in the ventral tegmental area that involves a switch of the subunit composition of AMPA receptors
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DOI：
10.1111/j.1460-9568.2005.03979.x
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发表时间：
2005-03-01
影响因子：
3.4
通讯作者：
Lüscher, C
中科院分区：
文献类型：
--
作者：
Bellone, C;Lüscher, C
腹侧被盖区(VTA)多巴胺(DA)神经元上的兴奋性谷氨酸能突触在自然奖赏的调节和药物暴露的反应中经历了长期的变化。有人认为，随后的语境依赖性行为变化与长时程增强(LTP)和长时程抑制(LTD)的平衡决定的突触传入的有效性增加有关。然而，所涉及的LTP/LTD形式的分子性质仍然难以捉摸。在这里，我们使用急性大鼠脑片，描述了一种形式的长期抑郁(LTD)，它由突触活动或激活I组代谢性谷氨酸受体(MGluR)的外源性激动剂参与，并对mGluR1拮抗剂敏感。在mGluR-LTD之前，AMPAR介导的兴奋性突触后电流(EPSCs)在正电位下表现出强烈的整流性，并且对缺乏GluR2的AMPAR的选择性阻断剂Joro蜘蛛毒素(JST)敏感。加入mGluR-LTD后，AMPAR EPSCs呈线性电流-电压关系，对JST不敏感。我们的结论是，mGluR1s的激活触发了含有AMPAR的GluR2天然受体的再分配，最终导致LTD，这可能反对病理性神经适应。
Excitatory glutamatergic synapses on dopamine (DA) neurons of the ventral tegmental area (VTA) undergo long-lasting changes during conditioning of natural rewards and in response to drug exposure. It has been suggested that the ensuing context-dependent behavioural changes are associated with an increased efficacy of synaptic afferents determined by the balance of long-term potentiation (LTP) and long-term depression (LTD). However, the molecular nature of the forms of LTP/LTD involved remains elusive. Here, using acute rat brain slices, we describe a form of long-term depression (LTD) that was engaged by synaptic activity or exogenous agonists activating group I metabotropic glutamate receptors (mGluR) and was sensitive to mGluR1 antagonists. Prior to mGluR-LTD, AMPAR mediated excitatory postsynaptic currents (EPSCs) showed strong rectification at positive potentials and were sensitive to Joro spider toxin (JST), a selective blocker of GluR2-lacking AMPARs. After mGluR-LTD, AMPAR EPSCs had linear current-voltage relations and became insensitive to JST. We conclude that activation of mGluR1s triggers a redistribution exchanging native receptors for GluR2 containing AMPARs, ultimately causing LTD that may oppose pathological neuroadaptation.