Chronic stress enhances synaptic plasticity due to disinhibition in the anterior cingulate cortex and induces hyper-locomotion in mice
Chronic stress enhances synaptic plasticity due to disinhibition in the anterior cingulate cortex and induces hyper-locomotion in mice
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DOI：
10.1016/j.neuropharm.2009.12.011
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发表时间：
2010-03-01
影响因子：
4.7
通讯作者：
Murakoshi, Takayuki
中科院分区：
文献类型：
--
作者：
Ito, Hiroshi;Nagano, Masatoshi;Murakoshi, Takayuki
前扣带皮层（ACC）参与了各种精神障碍的病理生理学，其中许多是由压力加剧。然而，很少有研究表明，压力引起的ACC突触功能的改变与情绪行为有关。我们研究了慢性束缚应激（CRS）对小鼠行为和ACC II/III层突触功能的影响。CRS小鼠的场兴奋性突触后电位（fEPSPs）的持续时间比对照小鼠长。在CRS小鼠中，通过全细胞膜片钳记录的微型抑制性突触后电流（mIPSC）的频率降低，而微型兴奋性突触后电流（mEPSC）保持不变。CRS患者fEPSP和诱发EPSC的配对脉冲比（PPR）较大。诱发的EPSC的NMDA成分在各组间无差异。CRS小鼠fEPSP的长时程增强（LTP）和长时程抑制均大于对照小鼠。荷包牡丹碱阻断GABA（A）受体后，fEPSP持续时间、PPRs和LTP水平无明显差异。与对照小鼠相比，CRS小鼠在旷场试验中表现出过度运动活动，而在亮/暗选择试验中，各组之间在焦虑样行为方面没有观察到差异。与对照小鼠相比，CRS小鼠在恐惧条件反射测试中表现出减少的冻结行为。这些发现表明，CRS通过GABA（A）受体信号传导的去抑制而增加兴奋性，促进ACC中的突触可塑性，这可能是CRS后诱导行为超运动活性的基础。(C)2009爱思唯尔有限公司保留所有权利。
The anterior cingulate cortex (ACC) is involved in the pathophysiology of a variety of mental disorders, many of which are exacerbated by stress. There are few studies, however, of stress-induced modification of synaptic function in the ACC that is relevant to emotional behavior. We investigated the effects of chronic restraint stress (CRS) on behavior and synaptic function in layers II/III of the ACC in mice. The duration of field excitatory postsynaptic potentials (fEPSPs) was longer in CRS mice than in control mice. The frequency of miniature inhibitory postsynaptic currents (mIPSCs) recorded by whole-cell patch-clamping was reduced in CRS mice, while miniature excitatory postsynaptic currents (mEPSCs) remained unchanged. Paired-pulse ratios (PPRs) of the fEPSP and evoked EPSC were larger in CRS. There was no difference in NMDA component of evoked EPSCs between the groups. Both long-term potentiation (LTP) and long-term depression of fEPSP were larger in CRS mice than in control mice. The differences between the groups in fEPSP duration, PPRs and LTP level were not observed when the GABA(A) receptor was blocked by bicuculline. Compared to control mice, CRS mice exhibited hyper-locomotive activity in an open field test, while no difference was observed between the groups in anxiety-like behavior in a light/dark choice test. CRS mice displayed decreased freezing behavior in fear conditioning tests compared to control mice. These findings suggest that CRS facilitates synaptic plasticity in the ACC via increased excitability due to disinhibition of GABA(A) receptor signalling, which may underlie induction of behavioral hyper-locomotive activity after CRS. (C) 2009 Elsevier Ltd. All rights reserved.