A Central Amygdala-Globus Pallidus Circuit Conveys Unconditioned Stimulus-Related Information and Controls Fear Learning

The central amygdala (CeA) is critically involved in a range of adaptive behaviors, including defensive behaviors. Neurons in the CeA send long-range projections to a number of extra-amygdala targets, but the functions of these projections remain elusive. Here, we report that a previously neglected CeA-to-globus pallidus external segment (GPe) circuit plays an essential role in classical fear conditioning. By anatomic tracing, in situ hybridization and channelrhodopsin (ChR2)-assisted circuit mapping in both male and female mice, we found that a subset of CeA neurons send projections to the GPe, and the major-ity of these GPe-projecting CeA neurons express the neuropeptide somatostatin. Notably, chronic inhibition of GPe-projecting CeA neurons with the tetanus toxin light chain (TeLC) completely blocks auditory fear conditioning. In vivo fiber photometry revealed that these neurons are selectively excited by the unconditioned stimulus (US) during fear conditioning. Furthermore, transient optogenetic inactivation or activation of these neurons selectively during US presentation impairs or promotes, respectively, fear learning. Our results suggest that a major function of GPe-projecting CeA neurons is to represent and convey US-related information through the CeA-GPe circuit, thereby regulating learning in fear conditioning.