In addition to being a major target and modulator of stress, the BLA is a critical node within the neural circuitry subserving learned fear behaviors. The BLA is activated during the formation, expression, and extinction of conditioned fear memories, and damage to the BLA disrupts one or more of these processes [79,80]. Implicating BLA ECB signaling in fear conditioning, several studies have shown that injecting a CB1R agonist (WIN55212-2) into the BLA enhanced the consolidation of conditioned fear (but impaired fear reconsolidation [81]), whereas CB1R antagonism/inverse agonism (AM251) had the opposite effect, impairing fear memory formation [82]. These effects on fear are not restricted to the BLA but involve a pathway between the BLA and mPFC. Responses to fear cues in mPFC neurons receiving inputs from BLA were potentiated by the CB1R agonist WIN55212-2, and CB1R blockade/inverse agonism (with AM251) in these regions disrupts fear learning and learning-related synaptic plasticity (long-term potentiation) [83–85].
