Prosapip1-Dependent Synaptic Adaptations in the Nucleus Accumbens Drive Alcohol Intake, Seeking, and Reward

Laguesse Sophie; Morisot Nadege; Shin Jung Hoon; Liu Feng; Adrover Martin F.; Sakhai Samuel A.; Lopez Marcelo F.; Phamluong Khanhky; Griffin William C. III; Becker Howard C.; Bender Kevin J.; Alvarez Veronica A.; Ron Dorit

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Prosapip1-Dependent Synaptic Adaptations in the Nucleus Accumbens Drive Alcohol Intake, Seeking, and Reward

机译：髓纸1依赖突触适应核心抵抗，驾驶酒精摄入，寻求和奖励

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The mammalian target of rapamycin complex 1 (mTORC1), a transducer of local dendritic translation, participates in learning and memory processes as well as in mechanisms underlying alcohol-drinking behaviors. Using an unbiased RNA-seq approach, we identified Prosapip1 as a novel downstream target of mTORC1 whose translation and consequent synaptic protein expression are increased in the nucleus accumbens (NAc) of mice excessively consuming alcohol. We demonstrate that alcohol-dependent increases in Prosapip1 levels promote the formation of actin filaments, leading to changes in dendritic spine morphology of NAc medium spiny neurons (MSNs). We further demonstrate that Prosapip1 is required for alcohol-dependent synaptic localization of GluA2 lacking AMPA receptors in NAc shell MSNs. Finally, we present data implicating Prosapip1 in mechanisms underlying alcohol self-administration and reward. Together, these data suggest that Prosapip1 in the NAc is a molecular transducer of structural and synaptic alterations that drive and/or maintain excessive alcohol use.

机译：哺乳动物催乳素复合物1（MTORC1）的哺乳动物靶标，局部树突翻译的换能器，参与学习和记忆过程以及酒精饮用行为的机制。使用无偏的RNA-SEQ方法，我们将PROSAPIP1鉴定为MTORC1的新型下游靶标，其平移和随后的突触蛋白表达在过量饮酒的小鼠的核心（NAc）中增加。我们证明，谷物植物依赖性增加的水平促进了肌动蛋白长丝的形成，导致NAC中等刺神经元（MSN）的树突状脊柱形态的变化。我们进一步证明了PROWAPIP1是缺乏NAC壳MSN中缺乏AMPA受体的GLUA2的醇依赖性突触定位所必需的。最后，我们展示了谷物自我管理和奖励的机制中暗示的数据。这些数据在一起表明NAC中的PROSAPIP1是结构和突触改变的分子传感器，其驱动和/或保持过量的酒精使用。

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《Neuron》 |2017年第1期|共23页
作者
Laguesse Sophie; Morisot Nadege; Shin Jung Hoon; Liu Feng; Adrover Martin F.; Sakhai Samuel A.; Lopez Marcelo F.; Phamluong Khanhky; Griffin William C. III; Becker Howard C.; Bender Kevin J.; Alvarez Veronica A.; Ron Dorit;
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作者单位

Univ Calif San Francisco Dept Neurol San Francisco CA 94143 USA;

Univ Calif San Francisco Dept Neurol San Francisco CA 94143 USA;

NIAAA Lab Neurobiol Compuls Behav US Natl Inst Hlth Bethesda MD USA;

Univ Calif San Francisco Dept Neurol San Francisco CA 94143 USA;

NIAAA Lab Neurobiol Compuls Behav US Natl Inst Hlth Bethesda MD USA;

Univ Calif San Francisco Dept Neurol San Francisco CA 94143 USA;

Med Univ South Carolina Dept Psychiat &

Behav Sci Charleston Alcohol Res Ctr 171 Ashley Ave;

Univ Calif San Francisco Dept Neurol San Francisco CA 94143 USA;

Med Univ South Carolina Dept Psychiat &

Behav Sci Charleston Alcohol Res Ctr 171 Ashley Ave;

Med Univ South Carolina Dept Psychiat &

Behav Sci Charleston Alcohol Res Ctr 171 Ashley Ave;

Univ Calif San Francisco Dept Neurol San Francisco CA 94143 USA;

NIAAA Lab Neurobiol Compuls Behav US Natl Inst Hlth Bethesda MD USA;

Univ Calif San Francisco Dept Neurol San Francisco CA 94143 USA;

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正文语种 eng
中图分类神经病学;
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1. Prosapip1-Dependent Synaptic Adaptations in the Nucleus Accumbens Drive Alcohol Intake, Seeking, and Reward [J] . Laguesse Sophie, Morisot Nadege, Shin Jung Hoon, Neuron . 2017,第1期

机译：髓纸1依赖突触适应核心抵抗，驾驶酒精摄入，寻求和奖励
2. EPISODIC SUCROSE INTAKE DURING FOOD RESTRICTION INCREASES SYNAPTIC ABUNDANCE OF AMPA RECEPTORS IN NUCLEUS ACCUMBENS AND AUGMENTS INTAKE OF SUCROSE FOLLOWING RESTORATION OF AD LIBITUM FEEDING [J] . Peng X. -X., Lister A., Rabinowitsch A., Neuroscience: An International Journal under the Editorial Direction of IBRO . 2015,第Null期

机译：食物限制过程中的异位蔗糖摄入增加了伏隔核中AMPA受体的突触丰度，并且在恢复AD雌性供体后增加了糖摄取
3. The origin of glutamatergic synaptic inputs controls synaptic plasticity and its modulation by alcohol in mice nucleus accumbens [J] . Xincai Ji, Sucharita Saha, Gilles E. Martin Frontiers in Synaptic Neuroscience . 2015,第3期

机译：谷氨酸能突触输入的起源控制小鼠伏隔核中突触可塑性及其受酒精的调节。
4. Cooperative role of the nucleus accumbens shell and core in behavioral adaptation to environmental change [C] . Miyazaki, K.W., Miyazaki, Engineering in Medicine and Biology Society, 2003. Proceedings of the 25th Annual International Conference of the IEEE . 2003

机译：伏伏核壳与核在行为适应环境变化中的协同作用
5. Drugs and Bugs: The Role of Toll-like Receptor 4 in Nucleus Accumbens Synaptic Physiology and Reward Behavior [D] . Kashima, Daniel Tetsunori 2019

机译：毒品和虫子：Toll样受体4在伏隔核突触生理和奖励行为中的作用。
6. Prosapip1-Dependent Synaptic Adaptations in the Nucleus Accumbens Drive Alcohol Intake Seeking and Reward [O] . Sophie Laguesse, Nadege Morisot, Jung Hoon Shin, -1

机译：Prosapip1依赖突触适应在伏隔核驱动酒精摄入寻求和奖励。
7. Prosapip1-Dependent Synaptic Adaptations in the Nucleus Accumbens Drive Alcohol Intake, Seeking, and Reward [O] . Sophie Laguesse, Nadege Morisot, Jung Hoon Shin, 2017

机译：PravaPip1依赖于核心突触的突触突扰会驱动酒精摄入，寻求和奖励

Prosapip1-Dependent Synaptic Adaptations in the Nucleus Accumbens Drive Alcohol Intake, Seeking, and Reward

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