The fear circuit of the mouse forebrain: connections between the mediodorsal thalamus, frontal cortices and basolateral amygdala.

A large forebrain circuit, including the thalamus, amygdala and frontal cortical regions, is responsible for the establishment and extinction of fear-related memories. Understanding interactions among these three regions is critical to deciphering the basic mechanisms of fear. With the advancement of molecular and optogenetics techniques, the mouse has become the main species used to study fear-related behaviours. However, the basic connectivity pattern of the forebrain circuits involved in processing fear has not been described in this species. In this study we mapped the connectivity between three key nodes of the circuit, i.e. the basolateral nucleus of the amygdala (BLA), the mediodorsal nucleus of the thalamus (MD) and the medial prefrontal cortex, which were shown to have closed triangular connectivity in rats. In contrast to rat, we found no evidence for this closed loop in mouse. There was no major input from the BLA to the MD and little overlap between medial prefrontal regions connected with both the BLA and MD. The common nodes in the frontal cortex, which displayed reciprocal connection with both the BLA and MD were the agranular insular cortex and the border zone of the cingulate and secondary motor cortex. In addition, the BLA can indirectly affect the MD via the orbital cortex. We attribute the difference between our results and earlier rat studies to methodological problems rather than to genuine species difference. Our data demonstrate that the BLA and MD communicate via cortical sectors, the roles in fear-related behaviour of which have not been extensively studied. In general, our study provides the morphological framework for studies of murine fear-related behaviours.