An insular cortex to lateral amygdala pathway in fear learning

During fear learning, associations between an aversive stimulus (the US), and a sensory cue (CS) are formed at specific brain synapses. Nevertheless, how US information is transmitted to brain areas involved in value processing, like the amygdala, is still elusive. Using optogenetics, in-vivo Ca2+ imaging, and circuit tracing, we investigate the role of the posterior insular cortex (pInsCx) and relevant output pathways of this cortical area in fear learning. Optogenetic suppression of US-signaling in pInsCx principal neurons compromises auditory-cued fear learning. The pInsCx makes a robust glutamatergic synapse in the lateral amygdala (LA), which undergoes long-term potentiation after fear learning, and transmits US-information to a sub-population of LA neurons. Suppressing US-signaling in LA-projectors recapitulates the fear learning deficits observed after silencing pInsCx principal neurons. Thus, the pInsCx, via a plastic output synapse, transmits US-information to the LA and critically contributes to the formation of auditory-cued fear memories.