A Neural Switch for Active and Passive Fear

SummaryThe central nucleus of the amygdala (CeA) serves as a major output of this structure and plays a critical role in the expression of conditioned fear. By combining cell- and tissue-specific pharmacogenetic inhibition with functional magnetic resonance imaging (fMRI), we identified circuits downstream of CeA that control fear expression in mice. Selective inhibition of a subset of neurons in CeA led to decreased conditioned freezing behavior and increased cortical arousal as visualized by fMRI. Correlation analysis of fMRI signals identified functional connectivity between CeA, cholinergic forebrain nuclei, and activated cortical structures, and cortical arousal was blocked by cholinergic antagonists. Importantly, inhibition of these neurons switched behavioral responses to the fear stimulus from passive to active responses. Our findings identify a neural circuit in CeA that biases fear responses toward either passive or active coping strategies.

► Suppression of selected cells in amygdala switches passive to active fear behavior
► Switch to active fear behavior depends on cholinergic forebrain neurons
► fMRI mapping can be used to identify neural circuits involved in fear
► Oxytocin receptor-expressing amygdala neurons are tonically inhibited at baseline