Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.
Neuropharmacology. 2010 Mar-Apr;58(4-5):746-57. doi: 10.1016/j.neuropharm.2009.12.011. Epub 2009 Dec 24.
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.
扣带前皮质（ACC）参与多种精神障碍的病理生理学，其中许多障碍会因应激而加重。然而，很少有研究关注应激对与情绪行为相关的 ACC 突触功能的影响。我们研究了慢性束缚应激（CRS）对小鼠 ACC 层 II/III 中行为和突触功能的影响。与对照组相比，CRS 小鼠的场兴奋性突触后电位（fEPSP）持续时间更长。全细胞膜片钳记录的抑制性小突触电流（mIPSCs）频率在 CRS 小鼠中降低，而兴奋性小突触电流（mEPSCs）保持不变。fEPSP 和诱发 EPSC 的成对脉冲比（PPR）在 CRS 中更大。两组之间的诱发 EPSC 的 NMDA 成分没有差异。与对照组相比，CRS 小鼠的 fEPSP 长时程增强（LTP）和长时程抑制（LTD）更大。当 GABA(A)受体被 Bicuculline 阻断时，两组之间在 fEPSP 持续时间、PPR 和 LTP 水平上的差异消失。与对照组相比，CRS 小鼠在旷场试验中表现出过度活跃的运动行为，而在明暗选择试验中两组之间的焦虑样行为没有差异。与对照组相比，CRS 小鼠在恐惧条件反射试验中表现出较少的冻结行为。这些发现表明，CRS 通过 GABA(A)受体信号去抑制导致的兴奋性增加促进了 ACC 中的突触可塑性，这可能是 CRS 后诱导行为过度活跃的基础。
