title: Cholinergic and serotonergic modulations differentially affect large-scale functional networks in the mouse brain.
abstract: Resting-state functional MRI (rsfMRI) is a widely implemented technique used to investigate large-scale topology in the human brain during health and disease. Studies in mice provide additional advantages, including the possibility to flexibly modulate the brain by pharmacological or genetic manipulations in combination with high-throughput functional connectivity (FC) investigations. Pharmacological modulations that target specific neurotransmitter systems, partly mimicking the effect of pathological events, could allow discriminating the effect of specific systems on functional network disruptions. The current study investigated the effect of cholinergic and serotonergic antagonists on large-scale brain networks in mice. The cholinergic system is involved in cognitive functions and is impaired in, e.g., Alzheimer's disease, while the serotonergic system is involved in emotional and introspective functions and is impaired in, e.g., Alzheimer's disease, depression and autism. Specific interest goes to the default-mode-network (DMN), which is studied extensively in humans and is affected in many neurological disorders. The results show that both cholinergic and serotonergic antagonists impaired the mouse DMN-like network similarly, except that cholinergic modulation additionally affected the retrosplenial cortex. This suggests that both neurotransmitter systems are involved in maintaining integrity of FC within the DMN-like network in mice. Cholinergic and serotonergic modulations also affected other functional networks, however, serotonergic modulation impaired the frontal and thalamus networks more extensively. In conclusion, this study demonstrates the utility of pharmacological rsfMRI in animal models to provide insights into the role of specific neurotransmitter systems on functional networks in neurological disorders.
authors.affiliation: Bio-Imaging Lab, University of Antwerp, Universiteitsplein 1, Wilrijk, 2610, Antwerp, Belgium. disha.shah@uantwerpen.be.
authors.forename: Disha
authors.initials: D
authors.lastname: Shah
authors.affiliation: Bio-Imaging Lab, University of Antwerp, Universiteitsplein 1, Wilrijk, 2610, Antwerp, Belgium.
authors.forename: Ines
authors.initials: I
authors.lastname: Blockx
authors.affiliation: Bio-Imaging Lab, University of Antwerp, Universiteitsplein 1, Wilrijk, 2610, Antwerp, Belgium.|Max Planck Institute for Biological Cybernetics, Spemannstrasse 38, 72076, Tübingen, Germany.
authors.forename: Georgios A
authors.initials: GA
authors.lastname: Keliris
authors.affiliation: Bio-Imaging Lab, University of Antwerp, Universiteitsplein 1, Wilrijk, 2610, Antwerp, Belgium.
authors.forename: Firat
authors.initials: F
authors.lastname: Kara
authors.affiliation: Bio-Imaging Lab, University of Antwerp, Universiteitsplein 1, Wilrijk, 2610, Antwerp, Belgium.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Jonckers
authors.affiliation: Bio-Imaging Lab, University of Antwerp, Universiteitsplein 1, Wilrijk, 2610, Antwerp, Belgium.
authors.forename: Marleen
authors.initials: M
authors.lastname: Verhoye
authors.affiliation: Bio-Imaging Lab, University of Antwerp, Universiteitsplein 1, Wilrijk, 2610, Antwerp, Belgium.
authors.forename: Annemie
authors.initials: A
authors.lastname: Van der Linden
mesh_terms: D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D001931:Brain Mapping; D006993:Hypnotics and Sedatives / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging; D008297:Male; D020926:Medetomidine / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D018727:Muscarinic Antagonists / Q000008:administration & dosage; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000008:administration & dosage; D011976:Receptors, Muscarinic / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*; D012601:Scopolamine / Q000008:administration & dosage; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000008:administration & dosage
chemical_list: D006993:Hypnotics and Sedatives; D018727:Muscarinic Antagonists; D010879:Piperazines; D011976:Receptors, Muscarinic; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C078730:serotonin 5 receptor; C081293:WAY 100135; D012701:Serotonin; D012601:Scopolamine; D020926:Medetomidine; D000109:Acetylcholine
keywords: Cholinergic; Default-mode network; Functional connectivity; Functional networks; Mouse brain; Serotonergic