title: A novel anesthesia regime enables neurofunctional studies and imaging genetics across mouse strains.
abstract: Functional magnetic resonance imaging (fMRI) has revolutionized neuroscience by opening a unique window that allows neurocircuitry function and pathological alterations to be probed non-invasively across brain disorders. Here we report a novel sustainable anesthesia procedure for small animal neuroimaging that overcomes shortcomings of anesthetics commonly used in rodent fMRI. The significantly improved preservation of cerebrovascular dynamics enhances sensitivity to neural activity changes for which it serves as a proxy in fMRI readouts. Excellent cross-species/strain applicability provides coherence among preclinical findings and is expected to improve translation to clinical fMRI investigations. The novel anesthesia procedure based on the GABAergic anesthetic etomidate was extensively validated in fMRI studies conducted in a range of genetically engineered rodent models of autism and strains commonly used for transgenic manipulations. Etomidate proved effective, yielded long-term stable physiology with basal cerebral blood flow of ~0.5 ml/g/min and full recovery. Cerebrovascular responsiveness of up to 180% was maintained as demonstrated with perfusion- and BOLD-based fMRI upon hypercapnic, pharmacological and sensory stimulation. Hence, etomidate lends itself as an anesthetic-of-choice for translational neuroimaging studies across rodent models of brain disorders.
authors.affiliation: Roche Pharmaceutical Research &Early Development, Neuroscience Discovery, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors.forename: Marija M
authors.initials: MM
authors.lastname: Petrinovic
authors.affiliation: Institute for Biomedical Engineering, University and ETH Zurich, Wolfgang-Pauli-Strasse 27, 8093 Zurich, Switzerland.
authors.forename: Georges
authors.initials: G
authors.lastname: Hankov
authors.affiliation: Institute for Biomedical Engineering, University and ETH Zurich, Wolfgang-Pauli-Strasse 27, 8093 Zurich, Switzerland.|Neuroscience Center Zurich, University and ETH Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Aileen
authors.initials: A
authors.lastname: Schroeter
authors.affiliation: Roche Pharmaceutical Research &Early Development, Neuroscience Discovery, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bruns
authors.affiliation: Institute for Biomedical Engineering, University and ETH Zurich, Wolfgang-Pauli-Strasse 27, 8093 Zurich, Switzerland.|Neuroscience Center Zurich, University and ETH Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.|Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Rudin
authors.affiliation: Roche Pharmaceutical Research &Early Development, Neuroscience Discovery, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: von Kienlin
authors.affiliation: Roche Pharmaceutical Research &Early Development, Neuroscience Discovery, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors.forename: Basil
authors.initials: B
authors.lastname: Künnecke
authors.affiliation: Roche Pharmaceutical Research &Early Development, Neuroscience Discovery, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mueggler
mesh_terms: D000758:Anesthesia; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D005045:Etomidate / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D020926:Medetomidine / Q000494:pharmacology; D051379:Mice; D059906:Neuroimaging; D051381:Rats; D013045:Species Specificity
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane; D020926:Medetomidine; D005045:Etomidate