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Alcohol-induced damage to the fimbria/fornix reduces hippocampal-prefrontal cortex connection during early abstinence

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 w...

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Main Authors: Pérez-Cervera, Laura (Author) , De Santis, Silvia (Author) , Marcos, Encarni (Author) , Ghorbanzad-Ghaziany, Zahra (Author) , Trouvé-Carpena, Alejandro (Author) , Selim, Mohamed Kotb (Author) , Pérez-Ramírez, Úrsula (Author) , Pfarr, Simone (Author) , Bach, Patrick (Author) , Halli, Patrick (Author) , Kiefer, Falk (Author) , Moratal, David (Author) , Kirsch, Peter (Author) , Sommer, Wolfgang H. (Author) , Canals, Santiago (Author)
Format: Article (Journal)
Language:English
Published: 2023
In: Acta Neuropathologica Communications
Year: 2023, Volume: 11, Pages: 1-21
ISSN:2051-5960
DOI:10.1186/s40478-023-01597-8
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1186/s40478-023-01597-8
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Author Notes:Laura Pérez-Cervera, Silvia De Santis, Encarni Marcos, Zahra Ghorbanzad-Ghaziany, Alejandro Trouvé-Carpena, Mohamed Kotb Selim, Úrsula Pérez-Ramírez, Simone Pfarr, Patrick Bach, Patrick Halli, Falk Kiefer, David Moratal, Peter Kirsch, Wolfgang H. Sommer and Santiago Canals

MARC

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520 |a 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. 
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