A prefrontal microcircuit computes trial-wise discount of reinforcement during threat learning in male mice

Threat learning requires rapid adaptation, but how the brain weights successive aversive experiences remains unclear. Here we show that many male mice exhibit delayed freezing acquisition during auditory fear conditioning. A trial-wise discount reinforcement learning model captured these dynamics through transient attenuation of early associative updating. Medial prefrontal neurons projecting to the periaqueductal gray constrained acquisition and subsequent cue-evoked freezing: inhibition increased freezing, whereas activation reduced it. Calcium imaging of individual neurons identified a subpopulation with delayed post-shock responses that declined during learning and predicted the model-derived discount-like variable. Temporally restricted inhibition implicated activity extending beyond the shock in constraining early acquisition. Local somatostatin interneurons showed increasing shock-evoked activity and provided inhibitory input to these projection neurons, suggesting a mechanism for relaxing this constraint. These findings link the trial-wise weighting of aversive experience to a prefrontal inhibitory microcircuit and provide a framework for understanding individual differences in threat memory formation. Neural mechanisms underlying threat learning are not fully understood. Here authors identify a prefrontal circuit that constrains early threat learning in male mice. Local inhibitory neurons may release this constraint, providing a mechanism for regulating how strongly each experience shapes memory.