Disynaptic specificity of serial information flow for conditioned fear

Memory encoding and retrieval rely on specific interactions across multiple brain areas. Although connections between individual brain areas have been extensively studied, the anatomical and functional specificity of neu-ronal circuit organization underlying information transfer across multiple brain areas remains unclear. Here, we combine transsynaptic viral tracing, optogenetic manipulations, and calcium dynamics recordings to dissect the multisynaptic functional connectivity of the amygdala. We identify a distinct basolateral amygdala (BLA) sub-population that connects disynaptically to the periaqueductal gray (PAG) via the central amygdala (CeA). This disynaptic pathway serves as a core circuit element necessary for the learning and expression of conditioned fear and exhibits learning-related plasticity. Together, our findings demonstrate the utility of multisynaptic ap-proaches for functional circuit analysis and indicate that disynaptic specificity may be a general feature of neu-ronal circuit organization.

Automated summary

Memory encoding and retrieval rely on specific interactions across multiple brain areas, but the anatomical and functional specificity of neuronal circuit organization underlying information transfer across these areas is still unclear.