Article (Scientific journals)
Prosapip1-Dependent Synaptic Adaptations in the Nucleus Accumbens Drive Alcohol Intake, Seeking, and Reward
Laguesse, Sophie; Morisot, N.; Shin, J. H. et al.
2017In Neuron, 96 (1), p. 145-159.e8
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Keywords :
Actin; Addiction; Alcohol; Dendritic spines; Plasticity; Prosapip1; AMPA receptor; GluA2 protein; Prosapip1 protein; ProSAPiP1 protein, mouse; Article; RNA sequence; RNA translation; Actin Cytoskeleton; Alcohol Drinking; Animals; Carrier Proteins; Drug-Seeking Behavior; Ethanol; Male; Membrane Proteins; Mice; Multiprotein Complexes; Neuronal Plasticity; Nucleus Accumbens; Receptors, AMPA; Reward; Self Administration; TOR Serine-Threonine Kinases
Abstract :
[en] 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. Laguesse et al. identified Prosapip1 as a novel downstream target of mTORC1 in the nucleus accumbens that promotes actin reorganization as well as morphological and synaptic alterations that in turn drive alcohol drinking and seeking behaviors. © 2017 Elsevier Inc.
Disciplines :
Neurology
Author, co-author :
Laguesse, Sophie  ;  Université de Liège - ULiège > Giga - Neurosciences
Morisot, N.;  Department of Neurology, University of California, San Francisco, CA, United States, N.M. Brains On-line LLC, South San Francisco, CA, United States
Shin, J. H.;  Laboratory on Neurobiology of Compulsive Behaviors, National Institute of Alcohol Abuse and Alcoholism, US National Institutes of Health, Bethesda, MD, United States
Liu, F.;  Department of Neurology, University of California, San Francisco, CA, United States, School of Life Sciences, Sun Yat-sen University, Guangzhou, China
Adrover, M. F.;  Laboratory on Neurobiology of Compulsive Behaviors, National Institute of Alcohol Abuse and Alcoholism, US National Institutes of Health, Bethesda, MD, United States
Sakhai, S. A.;  Department of Neurology, University of California, San Francisco, CA, United States
Lopez, M.
Phamluong, K.;  Department of Neurology, University of California, San Francisco, CA, United States
Griffin, W. C.;  III, Charleston Alcohol Research Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, United States
Becker, H. C.;  Charleston Alcohol Research Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, United States, Department of Neurosciences, Medical University of South Carolina, Charleston, SC, United States, RHJ Department of Veterans Affairs Medical Center, Charleston, SC, United States
Bender, K. J.;  Department of Neurology, University of California, San Francisco, CA, United States
Alvarez, V. A.;  Laboratory on Neurobiology of Compulsive Behaviors, National Institute of Alcohol Abuse and Alcoholism, US National Institutes of Health, Bethesda, MD, United States
Ron, D.;  Department of Neurology, University of California, San Francisco, CA, United States
More authors (3 more) Less
Language :
English
Title :
Prosapip1-Dependent Synaptic Adaptations in the Nucleus Accumbens Drive Alcohol Intake, Seeking, and Reward
Publication date :
September 2017
Journal title :
Neuron
ISSN :
0896-6273
eISSN :
1097-4199
Publisher :
Cell Press
Volume :
96
Issue :
1
Pages :
145-159.e8
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 04 February 2019

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