Functional deficiency of MHC class I enhances LTP and abolishes LTD in the nucleus accumbens of mice.
Functional deficiency of MHC class I enhances LTP and abolishes LTD in the nucleus accumbens of mice.
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DOI：
10.1371/journal.pone.0107099
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Nakahara D
中科院分区：
文献类型：
--
作者：
Edamura M;Murakami G;Meng H;Itakura M;Shigemoto R;Fukuda A;Nakahara D
主要组织相容性复合体I类(MHCI)分子最近被发现是突触可塑性的新调节因子。这些分子在大脑的不同区域都有表达，特别是在经历活性依赖性突触可塑性的区域，但它们在伏隔核(NAC)中的作用尚不清楚。在这项研究中，我们通过缺失β2-微球蛋白来研究MHCI功能的遗传破坏的影响，该基因缺失导致MHCI细胞表面表达不足。首先，我们证实了MHCI分子在野生型小鼠的NAC核心中表达。其次，我们用野生型和β-2-微球蛋白敲除小鼠的NAC核心切片进行了电生理记录。我们发现，低频刺激在野生型小鼠中诱导了长期的抑制，但在基因敲除小鼠中没有，而高频刺激在两种类型的小鼠中都诱导了长期的增强，在基因敲除小鼠中幅度更大。此外，我们还证明，基因敲除小鼠对可卡因表现出更持久的行为敏化，这是一种与NAC相关的行为。利用该模型，我们用SDS消化的冻裂复制品标记法分析了NAC核心中总AMPA受体及其亚基GluR1和GluR2的密度。反复暴露可卡因后，野生型小鼠GluR1密度增加，但总AMPA受体和GluR2水平无明显变化。相比之下，在反复接触可卡因后，在基因敲除小鼠中观察到总AMPA受体、GluR1和GluR2的密度增加。这些结果表明，MHCI的功能缺陷增强了由电刺激和药物刺激引起的突触增强。
Major histocompatibility complex class I (MHCI) molecules were recently identified as novel regulators of synaptic plasticity. These molecules are expressed in various brain areas, especially in regions undergoing activity-dependent synaptic plasticity, but their role in the nucleus accumbens (NAc) is unknown. In this study, we investigated the effects of genetic disruption of MHCI function, through deletion of β2-microblobulin, which causes lack of cell surface expression of MHCI. First, we confirmed that MHCI molecules are expressed in the NAc core in wild-type mice. Second, we performed electrophysiological recordings with NAc core slices from wild-type and β2-microglobulin knock-out mice lacking cell surface expression of MHCI. We found that low frequency stimulation induced long-term depression in wild-type but not knock-out mice, whereas high frequency stimulation induced long-term potentiation in both genotypes, with a larger magnitude in knock-out mice. Furthermore, we demonstrated that knock-out mice showed more persistent behavioral sensitization to cocaine, which is a NAc-related behavior. Using this model, we analyzed the density of total AMPA receptors and their subunits GluR1 and GluR2 in the NAc core, by SDS-digested freeze-fracture replica labeling. After repeated cocaine exposure, the density of GluR1 was increased, but there was no change in total AMPA receptors and GluR2 levels in wild-type mice. In contrast, following repeated cocaine exposure, increased densities of total AMPA receptors, GluR1 and GluR2 were observed in knock-out mice. These results indicate that functional deficiency of MHCI enhances synaptic potentiation, induced by electrical and pharmacological stimulation.
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DOI：
10.1073/pnas.89.10.4363
发表时间：
1992-05-15
影响因子：
11.1
作者：
DUDEK, SM;BEAR, MF
通讯作者：
BEAR, MF
影响因子：
25
作者：
Glynn, Marian W.;Elmer, Bradford M.;Garay, Paula A.;Liu, Xiao-Bo;Needleman, Leigh A.;El-Sabeawy, Faten;McAllister, A. Kimberley
通讯作者：
McAllister, A. Kimberley
影响因子：
16.2
作者：
Lüscher C;Malenka RC
通讯作者：
Malenka RC
影响因子：
5.3
作者：
Mapelli, Jonathan;D'Angelo, Egidio
通讯作者：
D'Angelo, Egidio
影响因子：
5.3
作者：
Antal, Miklos;Fukazawa, Yugo;Shigemoto, Ryuichi
通讯作者：
Shigemoto, Ryuichi