A dopamine-induced gene expression signature regulates neuronal function and cocaine response.

Autor:	Savell KE; Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA., Tuscher JJ; Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA., Zipperly ME; Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA., Duke CG; Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA., Phillips RA 3rd; Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA., Bauman AJ; Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA., Thukral S; Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA., Sultan FA; Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA., Goska NA; Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA., Ianov L; Civitan International Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA., Day JJ; Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.; Civitan International Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2020 Jun 24; Vol. 6 (26), pp. eaba4221. Date of Electronic Publication: 2020 Jun 24 (Print Publication: 2020).
DOI:	10.1126/sciadv.aba4221
Abstrakt:	Drugs of abuse elevate dopamine levels in the nucleus accumbens (NAc) and alter transcriptional programs believed to promote long-lasting synaptic and behavioral adaptations. Here, we leveraged single-nucleus RNA-sequencing to generate a comprehensive molecular atlas of cell subtypes in the NAc, defining both sex-specific and cell type-specific responses to acute cocaine experience in a rat model system. Using this transcriptional map, we identified an immediate early gene expression program that is up-regulated following cocaine experience in vivo and dopamine receptor activation in vitro. Multiplexed induction of this gene program with a large-scale CRISPR-dCas9 activation strategy initiated a secondary synapse-centric transcriptional profile, altered striatal physiology in vitro, and enhanced cocaine sensitization in vivo. Together, these results define the transcriptional response to cocaine with cellular precision and demonstrate that drug-responsive gene programs can potentiate both physiological and behavioral adaptations to drugs of abuse. (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
Databáze:	MEDLINE
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