Remodeling of Sensorimotor Brain Connectivity in Gpr88-Deficient Mice.

Autor:	Arefin TM; 1 Department of Radiology, Medical Physics, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg , Freiburg, Germany .; 2 Faculty of Biology, University of Freiburg , Freiburg, Germany .; 3 Bernstein Center Freiburg, University of Freiburg , Freiburg, Germany .; 4 Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine , New York, New York., Mechling AE; 1 Department of Radiology, Medical Physics, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg , Freiburg, Germany .; 2 Faculty of Biology, University of Freiburg , Freiburg, Germany ., Meirsman AC; 5 Département de Médecine Translationnelle et Neurogénétique, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U-964, CNRS UMR-7104, Université de Strasbourg , Illkirch-Graffenstaden, France .; 6 Neuroscience Paris Seine, Institut de Biologie Paris Seine , CNRS UMR 8246/INSERM U1130/Université Pierre et Marie Currie, Paris, France ., Bienert T; 1 Department of Radiology, Medical Physics, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg , Freiburg, Germany ., Hübner NS; 1 Department of Radiology, Medical Physics, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg , Freiburg, Germany .; 2 Faculty of Biology, University of Freiburg , Freiburg, Germany ., Lee HL; 1 Department of Radiology, Medical Physics, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg , Freiburg, Germany ., Ben Hamida S; 5 Département de Médecine Translationnelle et Neurogénétique, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U-964, CNRS UMR-7104, Université de Strasbourg , Illkirch-Graffenstaden, France .; 7 Douglas Mental Health Institute, Department of Psychiatry, McGill University , Montreal, Quebec, Canada ., Ehrlich A; 5 Département de Médecine Translationnelle et Neurogénétique, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U-964, CNRS UMR-7104, Université de Strasbourg , Illkirch-Graffenstaden, France .; 7 Douglas Mental Health Institute, Department of Psychiatry, McGill University , Montreal, Quebec, Canada ., Roquet D; 8 Engineering Science, Computer Science and Imaging Laboratory (ICube), Integrative Multimodal Imaging in Healthcare, University of Strasbourg-CNRS , Strasbourg, France ., Hennig J; 1 Department of Radiology, Medical Physics, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg , Freiburg, Germany ., von Elverfeldt D; 1 Department of Radiology, Medical Physics, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg , Freiburg, Germany ., Kieffer BL; 5 Département de Médecine Translationnelle et Neurogénétique, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U-964, CNRS UMR-7104, Université de Strasbourg , Illkirch-Graffenstaden, France .; 7 Douglas Mental Health Institute, Department of Psychiatry, McGill University , Montreal, Quebec, Canada ., Harsan LA; 1 Department of Radiology, Medical Physics, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg , Freiburg, Germany .; 8 Engineering Science, Computer Science and Imaging Laboratory (ICube), Integrative Multimodal Imaging in Healthcare, University of Strasbourg-CNRS , Strasbourg, France .; 9 Department of Biophysics and Nuclear Medicine, Faculty of Medicine, University Hospital Strasbourg , Strasbourg, France .
Jazyk:	angličtina
Zdroj:	Brain connectivity [Brain Connect] 2017 Oct; Vol. 7 (8), pp. 526-540.
DOI:	10.1089/brain.2017.0486
Abstrakt:	Recent studies have demonstrated that orchestrated gene activity and expression support synchronous activity of brain networks. However, there is a paucity of information on the consequences of single gene function on overall brain functional organization and connectivity and how this translates at the behavioral level. In this study, we combined mouse mutagenesis with functional and structural magnetic resonance imaging (MRI) to determine whether targeted inactivation of a single gene would modify whole-brain connectivity in live animals. The targeted gene encodes GPR88 (G protein-coupled receptor 88), an orphan G protein-coupled receptor enriched in the striatum and previously linked to behavioral traits relevant to neuropsychiatric disorders. Connectivity analysis of Gpr88-deficient mice revealed extensive remodeling of intracortical and cortico-subcortical networks. Most prominent modifications were observed at the level of retrosplenial cortex connectivity, central to the default mode network (DMN) whose alteration is considered a hallmark of many psychiatric conditions. Next, somatosensory and motor cortical networks were most affected. These modifications directly relate to sensorimotor gating deficiency reported in mutant animals and also likely underlie their hyperactivity phenotype. Finally, we identified alterations within hippocampal and dorsal striatum functional connectivity, most relevant to a specific learning deficit that we previously reported in Gpr88 -/- animals. In addition, amygdala connectivity with cortex and striatum was weakened, perhaps underlying the risk-taking behavior of these animals. This is the first evidence demonstrating that GPR88 activity shapes the mouse brain functional and structural connectome. The concordance between connectivity alterations and behavior deficits observed in Gpr88-deficient mice suggests a role for GPR88 in brain communication.
Databáze:	MEDLINE
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