Optogenetic stimulation of dentate gyrus engrams restores memory in Alzheimer's disease mice.
Optogenetic stimulation of dentate gyrus engrams restores memory in Alzheimer's disease mice.
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齿状回印迹的光遗传学刺激可恢复阿尔茨海默病小鼠的记忆。
DOI：
10.1002/hipo.22756
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发表时间：
2017-10
期刊：
影响因子：
3.5
通讯作者：
Denny CA
中科院分区：
文献类型：
--
作者：
Perusini JN;Cajigas SA;Cohensedgh O;Lim SC;Pavlova IP;Donaldson ZR;Denny CA
阿尔茨海默病（Alzheimer's disease，AD）是一种以β淀粉样蛋白（amyloid-beta，Aβ）斑块和tau神经元缠结为特征的神经退行性疾病。APPswe/PS1 dE 9（APP/PS1）小鼠已被开发为AD模型，其特征在于在4-6月龄时形成斑块。在这里，我们试图通过描述各种类型的记忆来更好地理解AD相关的认知衰退。为了更好地了解AD如何导致记忆力下降，APP/PS1小鼠与ArcCreERT 2小鼠进行了繁殖。在这条线上，在记忆编码期间激活的神经系综可以被不可磨灭地标记，并直接与在记忆检索期间激活的神经系综进行比较（即，记忆痕迹/痕迹）。我们首先对APP/PS1 × ArcCreERT 2 ×通道视紫红质（ChR 2）增强的黄色荧光蛋白（EYFP）小鼠进行了一系列测试，检查抑郁和焦虑样行为，以及空间，社交和认知记忆。然后在这些小鼠中光遗传学刺激齿状回（DG）神经系综以改善记忆障碍。AD小鼠在恐惧记忆方面有最广泛的差异，如通过背景恐惧条件反射（CFC）评估的，其伴随着受损的DG记忆痕迹。与对照（Ctrl）小鼠相比，代表CFC记忆的DG神经系综的光遗传学刺激在AD小鼠的适当背景下增加了记忆提取。此外，光遗传学刺激促进了先前在记忆编码期间激活的神经系综的重新激活。这些数据表明，激活先前学习的DG记忆痕迹可以挽救认知障碍，并指出DG操纵作为治疗AD中常见的记忆丧失的潜在靶点。
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques and tau neurofibrillary tangles. APPswe/PS1dE9 (APP/PS1) mice have been developed as an AD model and are characterized by plaque formation at 4-6 months of age. Here, we sought to better understand AD-related cognitive decline by characterizing various types of memory. In order to better understand how memory declines with AD, APP/PS1 mice were bred with ArcCreERT2 mice. In this line, neural ensembles activated during memory encoding can be indelibly tagged and directly compared with neural ensembles activated during memory retrieval (i.e., memory traces/engrams). We first administered a battery of tests examining depressive- and anxiety-like behaviors, as well as spatial, social, and cognitive memory to APP/PS1 × ArcCreERT2 × channelrhodopsin (ChR2)-enhanced yellow fluorescent protein (EYFP) mice. Dentate gyrus (DG) neural ensembles were then optogenetically stimulated in these mice to improve memory impairment. AD mice had the most extensive differences in fear memory, as assessed by contextual fear conditioning (CFC), which was accompanied by impaired DG memory traces. Optogenetic stimulation of DG neural ensembles representing a CFC memory increased memory retrieval in the appropriate context in AD mice when compared with control (Ctrl) mice. Moreover, optogenetic stimulation facilitated reactivation of the neural ensembles that were previously activated during memory encoding. These data suggest that activating previously learned DG memory traces can rescue cognitive impairments and point to DG manipulation as a potential target to treat memory loss commonly seen in AD.
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影响因子：
64.5
作者：
Oury F;Khrimian L;Denny CA;Gardin A;Chamouni A;Goeden N;Huang YY;Lee H;Srinivas P;Gao XB;Suyama S;Langer T;Mann JJ;Horvath TL;Bonnin A;Karsenty G
通讯作者：
Karsenty G
影响因子：
64.8
作者：
Roy DS;Arons A;Mitchell TI;Pignatelli M;Ryan TJ;Tonegawa S
通讯作者：
Tonegawa S
影响因子：
25
作者：
通讯作者：
--
影响因子：
16.2
作者：
Denny CA;Kheirbek MA;Alba EL;Tanaka KF;Brachman RA;Laughman KB;Tomm NK;Turi GF;Losonczy A;Hen R
通讯作者：
Hen R
影响因子：
2.6
作者：
Gallo DA;Foster KT;Wong JT;Bennett DA
通讯作者：
Bennett DA