The lateralized LC-NAergic system distinguishes vicarious versus direct fear in mice

Fear can be induced either directly through self-experience of aversive events or vicariously by observing conspecifics experiencing such events. The locus coeruleus-norepinephrine (LC-NA) system is crucial in fear responses and cognitive processes. We investigated whether the LC-NA system differentially processes these two types of fear, direct and vicarious in male mice. The results highlighted that the right hemisphere LC→anterior cingulate cortex pathway is uniquely crucial for vicarious fear, while the two inputs to the LC-from the bed nucleus of the stria terminalis (BNST) and the central amygdala (CeA)-differentially contribute to fear processing. The BNST plays a more targeted role in vicarious fear, and the CeA has a broader influence on fear in general. This underscores the complexity and specialization within the LC-NA system for fear-processing.