摘要
小白蛋白(PV)在海马的阳性神经元在动物记忆中扮演着重要的角色,如空间工作记忆。然而,在海马区中间神经元的阳性小白蛋白如何影响动物行为尚不明确。在这里,我们使用设计受体实现了PV阳性中间神经元特异性和可逆性激活PV阳性中间神经元受体并完全由设计药物(DREADD)技术激活。DREADD诱导表达被体外培养神经元证明,其中的 hM3D-Gq-mCherry 的共转染与CRE质粒成向量导致对 hM3Dq 配体clozapine-N-oxide (CNO) 刺激的细胞反应。此外,齿状回(DG)PV-Cre小鼠接受双侧对照慢病毒注射或慢病毒表达双液氧hM3D-Gq-mCherry注射。在DG PV阳性中间神经元的选择性激活不影响小鼠自发活动或抑郁相关行为。有趣的是,PV阳性神经元所刺激引起的抗焦虑作用。激活PV中间神阳性经元似乎损害社会互动的新颖性,但对社会动机没有影响。然而,这种缺陷可能是由于其作为小鼠表达hM3DGq探索行为显著增加抗焦虑作用。小鼠表达hM3D-Gq不影响新物体识别。在DG的PV阳性神经元的激活保持完整的线索和恐惧记忆,但有利于恐惧消失。总的来说,我们的研究结果表明,在DG PV中间神经元活动的适当的控制对焦虑的调节、社会互动和恐惧消退至关重要。这些结果提高我们对PV阳性中间神经元在海马的生理作用有基本的了解。
关键词: 小白蛋白阳性的中间神经元,海马,Cre转基因小鼠,DREADD,社会记忆,识别记忆。
Current Molecular Medicine
Title:DREADD in Parvalbumin Interneurons of the Dentate Gyrus Modulates Anxiety, Social Interaction and Memory Extinction
Volume: 16 Issue: 1
Author(s): D. Zou, L. Chen, D. Deng, D. Jiang, F. Dong, C. McSweeney, Y. Zhou, L. Liu, G. Chen, Y. Wu and Y. Mao
Affiliation:
关键词: 小白蛋白阳性的中间神经元,海马,Cre转基因小鼠,DREADD,社会记忆,识别记忆。
摘要: Parvalbumin (PV)-positive interneurons in the hippocampus play a critical role in animal memory, such as spatial working memory. However, how PV-positive interneurons in the subregions of the hippocampus affect animal behaviors remains poorly defined. Here, we achieved specific and reversible activation of PV-positive interneurons using designer receptors exclusively activated by designer drugs (DREADD) technology. Inducible DREADD expression was demonstrated in vitro in cultured neurons, in which co-transfection of the hM3D-Gq-mCherry vector with a Cre plasmid resulted in a cellular response to hM3Dq ligand clozapine-N-oxide (CNO) stimulation. In addition, the dentate gyrus (DG) of PV-Cre mice received bilateral injection of control lentivirus or lentivirus expressing double floxed hM3D-Gq-mCherry. Selective activation of PV-positive interneurons in the DG did not affect locomotor activity or depression-related behavior in mice. Interestingly, stimulation of PV-positive interneurons induced an anxiolytic effect. Activation of PVpositive interneurons appears to impair social interaction to novelty, but has no effect on social motivation. However, this defect is likely due to the anxiolytic effect as the exploratory behavior of mice expressing hM3DGq is significantly increased. Mice expressing hM3D-Gq did not affect novel object recognition. Activation of PV-positive interneurons in the DG maintains intact cued and contextual fear memory but facilitates fear extinction. Collectively, our results demonstrated that proper control of PV interneurons activity in the DG is critical for regulation of the anxiety, social interaction and fear extinction. These results improve our fundamental understanding of the physiological role of PV-positive interneurons in the hippocampus.
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D. Zou, L. Chen, D. Deng, D. Jiang, F. Dong, C. McSweeney, Y. Zhou, L. Liu, G. Chen, Y. Wu and Y. Mao , DREADD in Parvalbumin Interneurons of the Dentate Gyrus Modulates Anxiety, Social Interaction and Memory Extinction, Current Molecular Medicine 2016; 16 (1) . https://dx.doi.org/10.2174/1566524016666151222150024
DOI https://dx.doi.org/10.2174/1566524016666151222150024 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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