Fear induced neuronal alterations in a genetic model of depression: an fMRI study on awake animals

Abstract

Previous human imaging studies used facial stimuli to explore the potential association between depression and fear. This study aimed at investigating brain alterations in a rodent model of depression when innate fear was induced in the form of the predator odor trimethylthiazoline (TMT). Flinders sensitive line (FSL) rats, a genetic animal model of depression, and their control counterpart Flinders resistant line (FRL), were used in this functional magnetic resonance imaging (fMRI) assessment. Compared to FRL, FSL rats exhibited greater BOLD activation in the cortical amygdala and hypoactivation in the prefrontal cortex in response to TMT, suggesting cortico-amygdalar dysfunction in the depressed strain. In addition, the hyperactivation in the insular cortex in FSL rats may be the basis for enhanced neuronal responses to fear and aversion in depression. These results are evidence for the value of translational models of depression in expanding understanding of the neural circuitries sub-serving common human co-morbidities like depression and fear.

Figure 1

Regional BOLD signal changes in FRL (n=8) and FSL (n=8) rats in response to lemon, with errors of mean. Single factor ANOVA was performed to evaluate significance. No significant difference was shown between the two groups in their response to lemon.

Figure 2

(A) BOLD signal changes in brain areas of FRL (n=8) and FSL (n=8) rats in response to TMT odor, with errors of mean. Higher activation from the FSL group was found in cortical amygdala and insular cortex, and lower activation in the prefrontal cortex. *: p<0.05; **: p<0.02. (B) Time course for the cortical nucleus of amygdala. (C) Time course for the prefrontal cortex.

Figure 3

TMT-elicited BOLD percent activation maps across the brain of FRL and FSL animals, overlaid on a fully segmented rat brain atlas. Each numbered slice is corresponding to the slices marked in the 3D atlas side view (based on a student t-test, thresholded at p<0.05).