In humans, functional magnetic resonance imaging (fMRI) has proved invaluable in delineating neural systems underlying sensory processing and higher cognitive and emotional functions. 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. We have previously demonstrated that prepubertal stress programmes increased learned fear behaviors in adult rats. This is accompanied by increased activation of key components of the fear-associated neural circuitry in the brain (eg. Amygdala) (Brydges et al 2013), determined by awake fMRI using a cued-fear conditioning protocol. Here we translate this methodology to mice, to enable exploitation of genetically modified mouse lines available with signaling in components of the HPA axis.
Acclimation to the scanning environment was optimized to reduce stress and head movement during scanning. Acclimated mice (C57bl/6) were conditioned to associate a flashing light (CS) with footshock (US) (paired group, PG) and a further group of mice received footshock and flashing light but explicitly not paired together (unpaired group, UG). Brain activation (BOLD signal) in response to the flashing light was measured 24hrs later in awake mice in the PG and UG using fMRI.
Activation of neural systems implicated in fear processing (amygdala, hypothalamus and perirhinal cortex) were identified in the PG, but activation of this circuitry was not present in the UG. Interestingly, a component of the reward pathway was activated in the UG (nucleus accumbens), suggesting that the safety of the CS was rewarding in the UG. Hence, we successfully imaged activation of fear circuitry in awake naïve mice and now can determine whether these networks are altered in mice carrying genetic modifications in corticosteroid receptor expression.
Brydges, N. M. et al (2013). PLoS One 8(1): e54197
Supported by a WISSF award and the Royal Society