Alcohol-induced damage to the fimbria/fornix reduces hippocampal-prefrontal cortex connection during early abstinence.
AUD
Alcohol
Cognitive test
DTI
Diffusion
Fimbria
Flexibility
Fornix
Hippocampus
Memory
Prefrontal cortex
TMT
White matter
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
21 06 2023
21 06 2023
Historique:
received:
09
05
2023
accepted:
30
05
2023
medline:
23
6
2023
pubmed:
22
6
2023
entrez:
21
6
2023
Statut:
epublish
Résumé
Alcohol dependence is characterized by a gradual reduction in cognitive control and inflexibility to contingency changes. The neuroadaptations underlying this aberrant behavior are poorly understood. Using an animal model of alcohol use disorders (AUD) and complementing diffusion-weighted (dw)-MRI with quantitative immunohistochemistry and electrophysiological recordings, we provide causal evidence that chronic intermittent alcohol exposure affects the microstructural integrity of the fimbria/fornix, decreasing myelin basic protein content, and reducing the effective communication from the hippocampus (HC) to the prefrontal cortex (PFC). Using a simple quantitative neural network model, we show how disturbed HC-PFC communication may impede the extinction of maladaptive memories, decreasing flexibility. Finally, combining dw-MRI and psychometric data in AUD patients, we discovered an association between the magnitude of microstructural alteration in the fimbria/fornix and the reduction in cognitive flexibility. Overall, these findings highlight the vulnerability of the fimbria/fornix microstructure in AUD and its potential contribution to alcohol pathophysiology. Fimbria vulnerability to alcohol underlies hippocampal-prefrontal cortex dysfunction and correlates with cognitive impairment.
Identifiants
pubmed: 37344865
doi: 10.1186/s40478-023-01597-8
pii: 10.1186/s40478-023-01597-8
pmc: PMC10286362
doi:
Substances chimiques
Ethanol
3K9958V90M
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101Informations de copyright
© 2023. The Author(s).
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