An insular cortex to lateral amygdala pathway in fear learning

Abstract

SummaryDuring 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-vivoCa2+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.