@article{e6919f1af0194df59113011223e87ac8,
title = "Dissecting Brain Networks Underlying Alcohol Binge Drinking Using a Systems Genomics Approach",
abstract = "Alcohol use disorder (AUD) is a complex psychiatric disorder with strong genetic and environmental risk factors. We studied the molecular perturbations underlying risky drinking behavior by measuring transcriptome changes across the neurocircuitry of addiction in a genetic mouse model of binge drinking. Sixteen generations of selective breeding for high blood alcohol levels after a binge drinking session produced global changes in brain gene expression in alcohol-na{\"i}ve High Drinking in the Dark (HDID-1) mice. Using gene expression profiles to generate circuit-level hypotheses, we developed a systems approach that integrated regulation of gene coexpression networks across multiple brain regions, neuron-specific transcriptional signatures, and knowledgebase analytics. Whole-cell, voltage-clamp recordings from nucleus accumbens shell neurons projecting to the ventral tegmental area showed differential ethanol-induced plasticity in HDID-1 and control mice and provided support for one of the hypotheses. There were similarities in gene networks between HDID-1 mouse brains and postmortem brains of human alcoholics, suggesting that some gene expression patterns associated with high alcohol consumption are conserved across species. This study demonstrated the value of gene networks for data integration across biological modalities and species to study mechanisms of disease.",
keywords = "Binge drinking, Gene expression, Gene networks, HDID mice, Transcriptome",
author = "Ferguson, {Laura B.} and Lingling Zhang and Daniel Kircher and Shi Wang and Mayfield, {R. Dayne} and Crabbe, {John C.} and Morrisett, {Richard A.} and Harris, {R. Adron} and Igor Ponomarev",
note = "Funding Information: This research was supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) grants AA012404 to RAH; AA020926 and AA016648 to RDM; AA020683 to IP, RAH, and RDM; AA013519 to JCC; AA013517 to Integrative Neuroscience Initiative on Alcoholism; AA017234 to IP; AA024332 to LBF; and the Department of Veterans Affairs (DVA) grant BX000313 to JCC. Neither funding agency had any role in study design, data collection/analysis, decision to publish, or preparation of the manuscript. LZ and SW are currently affiliated with the Key Laboratory of Marine Genetics and Breeding (Ocean University of China), the Ministry of Education (Qingdao 266003, China), and the Laboratory for Marine Biology and Biotechnology and the Qingdao National Laboratory for Marine Science and Technology, (Qingdao 266071, China). We thank Dr. Jody Mayfield for helpful comments and editing the manuscript. Funding Information: Acknowledgements This research was supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) grants AA012404 to RAH; AA020926 and AA016648 to RDM; AA020683 to IP, RAH, and RDM; AA013519 to JCC; AA013517 to Integrative Neuroscience Initiative on Alcoholism; AA017234 to IP; AA024332 to LBF; and the Department of Veterans Affairs (DVA) grant BX000313 to JCC. Neither funding agency had any role in study design, data collection/analysis, decision to publish, or preparation of the manuscript. LZ and SW are currently affiliated with the Key Laboratory of Marine Genetics and Breeding (Ocean University of China), the Ministry of Education (Qingdao 266003, China), and the Laboratory for Marine Biology and Biotechnology and the Qingdao National Laboratory for Marine Science and Technology, (Qingdao 266071, China). We thank Dr. Jody Mayfield for helpful comments and editing the manuscript. Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2019",
month = apr,
day = "1",
doi = "10.1007/s12035-018-1252-0",
language = "English (US)",
volume = "56",
pages = "2791--2810",
journal = "Molecular Neurobiology",
issn = "0893-7648",
publisher = "Humana Press",
number = "4",
}