Locarno, Nava, Barsotti et al. define a fronto-coerulear anatomical-functional loop under endocannabinoid (eCB) negative feedback that regulates contextual discrimination. Prefrontal cortex (PFC) inputs drive locus coeruleus (LC) norepinephrine (NE) release to enhance cortical firing, while locally mobilized eCBs weaken PFC to LC synapses, constraining NE-dependent entrainment of PFC neuronal assemblies.
