title: Imaging learned fear circuitry in awake mice using fMRI.
abstract: Functional magnetic resonance imaging (fMRI) of learned behaviour in 'awake rodents' provides the opportunity for translational preclinical studies into the influence of pharmacological and genetic manipulations on brain function. fMRI has recently been employed to investigate learned behaviour in awake rats. Here, this methodology is translated to mice, so that future fMRI studies may exploit the vast number of genetically modified mouse lines that are available. One group of mice was conditioned to associate a flashing light (conditioned stimulus, CS) with foot shock (PG; paired group), and another group of mice received foot shock and flashing light explicitly unpaired (UG; unpaired group). The blood oxygen level-dependent signal (proxy for neuronal activation) in response to the CS was measured 24 h later in awake mice from the PG and UG using fMRI. The amygdala, implicated in fear processing, was activated to a greater degree in the PG than in the UG in response to the CS. Additionally, the nucleus accumbens was activated in the UG in response to the CS. Because the CS signalled an absence of foot shock in the UG, it is possible that this region is involved in processing the safety aspect of the CS. To conclude, the first use of fMRI to visualise brain activation in awake mice that are completing a learned emotional task is reported. This work paves the way for future preclinical fMRI studies to investigate genetic and environmental influences on brain function in transgenic mouse models of disease and aging.
authors.affiliation: BHF Centre for Cardiovascular Sciences, QMRI, University of Edinburgh, Edinburgh, EH16 4TJ, UK.|Centre for Cognitive Ageing and Cognitive Epidemiology, QMRI, University of Edinburgh, Edinburgh, UK.
authors.forename: Anjanette P
authors.initials: AP
authors.lastname: Harris
authors.affiliation: BHF Centre for Cardiovascular Sciences, QMRI, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Lennen
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, QMRI, University of Edinburgh, Edinburgh, UK.|Neuroimaging Sciences, Centre for Clinical Brain Sciences, Edinburgh, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Marshall
authors.affiliation: BHF Centre for Cardiovascular Sciences, QMRI, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
authors.forename: Maurits A
authors.initials: MA
authors.lastname: Jansen
authors.affiliation: Neuroimaging Sciences, Centre for Clinical Brain Sciences, Edinburgh, UK.
authors.forename: Cyril R
authors.initials: CR
authors.lastname: Pernet
authors.affiliation: Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.
authors.forename: Nichola M
authors.initials: NM
authors.lastname: Brydges
authors.affiliation: Integrative Physics, University of Edinburgh, Edinburgh, UK.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Duguid
authors.affiliation: BHF Centre for Cardiovascular Sciences, QMRI, University of Edinburgh, Edinburgh, EH16 4TJ, UK.|Centre for Cognitive Ageing and Cognitive Epidemiology, QMRI, University of Edinburgh, Edinburgh, UK.
authors.forename: Megan C
authors.initials: MC
authors.lastname: Holmes
mesh_terms: D000818:Animals; D001245:Association Learning / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000502:physiology; D003213:Conditioning, Psychological / Q000502:physiology*; D004597:Electroshock; D005239:Fear / Q000502:physiology*; D005240:Feasibility Studies; D005528:Foot; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008810:Mice, Inbred C57BL; D009038:Motion; D009434:Neural Pathways / Q000502:physiology; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation; D012815:Signal Processing, Computer-Assisted; D014796:Visual Perception / Q000502:physiology; D014851:Wakefulness
chemical_list: D010100:Oxygen
keywords: Pavlovian conditioning; amygdala; awake mouse fMRI; cued fear conditioning; nucleus accumbens