How many brain regions are needed to elucidate the neural bases of fear and anxiety?

We suggest that to understand complex behaviors associated with fear and anxiety, we need to understand brain processes at the collective, network level. But what should be the type and spatial scale of the targeted circuits/networks? Not only are multi-region interactions essential—including complex reciprocal interactions, loops, and other types of arrangement—but it is profitable to characterize circuits spanning the entire neuroaxis. In particular, it is productive to conceptualize the circuits contributing to fear/anxiety as embedded into large-scale connectional systems. We discuss circuits involving the basolateral amygdala that contribute to aversive conditioning and fear extinction. In addition, we highlight the importance of the extended amygdala (central nucleus of the amygdala and bed nucleus of the stria terminalis) cortical-subcortical loop, which allows large swaths of cortex and subcortex to influence fear and anxiety. In this manner, fear/anxiety can be understood not only based on traditional “descending” mechanisms involving the hypothalamus and brainstem, but in terms of a considerably broader reentrant organization.