AMPA receptor-mediated miniature EPSCs have heterogeneous time courses in orexin neurons
AMPA receptor-mediated miniature EPSCs have heterogeneous time courses in orexin neurons
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DOI：
10.1016/j.bbrc.2010.08.132
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发表时间：
2010-10-01
影响因子：
3.1
通讯作者：
Hirasawa, Michiru
中科院分区：
文献类型：
--
作者：
Alberto, Christian O.;Hirasawa, Michiru
谷氨酸在调节食欲素神经元的活动中发挥着主导作用，这些神经元协调动机行为、睡眠-觉醒周期和自主功能。为了更深入地了解向食欲素神经元的兴奋性传递的特性，在大鼠脑切片中进行了全细胞膜片钳记录，并对药理学分离的微型兴奋性突触后电流（mEPSC）进行了定量分析。在超过一半的食欲素神经元中，mEPSC 表现出异质的时间进程：一些 mEPSC 具有快速的上升和衰减（快 mEPSC），而一些 mEPSC 具有更长的动力学、更小的振幅但更大的积分面积（慢 mEPSC）。其他食欲素神经元表现出低频 mEPSC，具有均匀、快速的动力学。在前者中，10-90%上升时间的分布直方图显示两个峰值，表明快和慢的mEPSC是不同的亚组。有时快和慢的 EPSC 会相加，这表明它们来自不同对的活性区和突触后受体簇。绝大多数 mEPSC 由对 GYKI 52466 和 DNQX 敏感的 AMPA 受体介导。为了确定产生快速和慢速 mEPSC 的突触是否受到差异调节，对 D1 和 D2 样激动剂的 mEPSC 的各种参数进行了测试。正如之前报道的，激动剂改变了频率，但对 mEPSC 的上升、衰减或面积没有影响，这表明多巴胺对快速和慢速 mEPSC 的影响相同。考虑到 EPSC 时间过程对突触整合的潜在生理影响，我们的研究提出了一个有趣的可能性，即兴奋性突触输入的不同子集被食欲素神经元以不同的方式处理。 (c) 2010 Elsevier Inc. 保留所有权利。
Glutamate plays a predominant role in regulating the activity of orexin neurons that coordinate motivated behaviors, sleep-wake cycle and autonomic functions. To gain more insight into the properties of excitatory transmission to orexin neurons, whole cell patch clamp recordings were made in rat brain slices and quantal analysis of pharmacologically isolated miniature excitatory postsynaptic currents (mEPSCs) was performed. In more than half the orexin neurons examined, mEPSCs showed heterogeneous time course: some mEPSCs had fast rise and decay (fast mEPSC), while some had longer kinetics, smaller amplitude but larger integrated area (slow mEPSC). Other orexin neurons showed low frequency mEPSCs with uniform, fast kinetics. In the former, distribution histogram of 10-90% rise time displayed two peaks, indicating that fast and slow mEPSCs are distinct subgroups. Occasionally fast and slow EPSCs would summate, suggesting that they arise from different pairs of active zones and postsynaptic receptor clusters. A large majority of mEPSCs were mediated by AMPA receptors that are sensitive to GYKI 52466 and DNQX. To determine whether synapses that give rise to fast and slow mEPSCs are differentially modulated, the D1- and D2-like agonists were tested on various parameters of mEPSCs. The agonists altered the frequency as previously reported, but had no effect on the rise, decay or area of mEPSC, suggesting that dopamine affects fast and slow mEPSCs equally. Given the potential physiological impact of EPSC time course on synaptic integration, our study raises an interesting possibility that distinct subset of excitatory synaptic inputs are processed differently by orexin neurons. (c) 2010 Elsevier Inc. All rights reserved.