Imaging learned fear circuitry in awake mice using fMRI.

Eur J Neurosci. 2015 May 5;

Authors: Harris AP, Lennen RJ, Marshall I, Jansen MA, Pernet CR, Brydges NM, Duguid IC, Holmes MC

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 we translate this methodology 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 (paired group) and another group of mice received foot shock and flashing light explicitly unpaired (unpaired group). The blood oxygenation level dependent signal (proxy for neuronal activation) in response to the CS was measured 24 h later in awake mice from the paired and unpaired group using fMRI. The amygdala, implicated in fear processing, was activated to a greater degree in the paired than in the unpaired group in response to the CS. Additionally, the nucleus accumbens was activated in the unpaired group in response to the CS. Since the CS signalled an absence of foot shock in the unpaired group, it is possible that this region is involved in processing the safety aspect of the CS. To conclude, we report the first use of fMRI to visualise brain activation in awake mice that are completing a learned emotional task. 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. This article is protected by copyright. All rights reserved.

PMID: 25943794 [PubMed - as supplied by publisher]