Brain-wide functional architecture remodeling by alcohol dependence and abstinence.
Fos
dependence
graph theory
iDISCO
network analysis
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
28 01 2020
28 01 2020
Historique:
pubmed:
16
1
2020
medline:
2
6
2020
entrez:
16
1
2020
Statut:
ppublish
Résumé
Alcohol abuse and alcohol dependence are key factors in the development of alcohol use disorder, which is a pervasive societal problem with substantial economic, medical, and psychiatric consequences. Although our understanding of the neurocircuitry that underlies alcohol use has improved, novel brain regions that are involved in alcohol use and novel biomarkers of alcohol use need to be identified. The present study used a single-cell whole-brain imaging approach to 1) assess whether abstinence from alcohol in an animal model of alcohol dependence alters the functional architecture of brain activity and modularity, 2) validate our current knowledge of the neurocircuitry of alcohol abstinence, and 3) discover brain regions that may be involved in alcohol use. Alcohol abstinence resulted in the whole-brain reorganization of functional architecture in mice and a pronounced decrease in modularity that was not observed in nondependent moderate drinkers. Structuring of the alcohol abstinence network revealed three major brain modules: 1) extended amygdala module, 2) midbrain striatal module, and 3) cortico-hippocampo-thalamic module, reminiscent of the three-stage theory. Many hub brain regions that control this network were identified, including several that have been previously overlooked in alcohol research. These results identify brain targets for future research and demonstrate that alcohol use and dependence remodel brain-wide functional architecture to decrease modularity. Further studies are needed to determine whether the changes in coactivation and modularity that are associated with alcohol abstinence are causal features of alcohol dependence or a consequence of excessive drinking and alcohol exposure.
Identifiants
pubmed: 31937658
pii: 1909915117
doi: 10.1073/pnas.1909915117
pmc: PMC6994986
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2149-2159Subventions
Organisme : NIAAA NIH HHS
ID : P50 AA006420
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA026685
Pays : United States
Organisme : NIAAA NIH HHS
ID : K99 AA027301
Pays : United States
Organisme : NIAAA NIH HHS
ID : R21 AA024198
Pays : United States
Organisme : NIAAA NIH HHS
ID : P60 AA006420
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA026081
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA022977
Pays : United States
Organisme : NINDS NIH HHS
ID : F31 NS108665
Pays : United States
Organisme : NIAAA NIH HHS
ID : T32 AA007456
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS079698
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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