TY - JOUR T1 - Hippocampal-amygdala interactions mediate uncertainty-dependent resistance to extinction following fear conditioning JF - bioRxiv DO - 10.1101/725648 SP - 725648 AU - John Morris AU - Francois Windels AU - Pankaj Sah Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/08/05/725648.abstract N2 - The partial reinforcement extinction effect (PREE) is a paradoxical learning phenomenon in which omission of reinforcement during acquisition results in more persistent conditioned responding in extinction. Here, we report a significant PREE with an inverted-U, entropy-like distribution against reinforcement probability following tone foot shock fear conditioning in rats, which was associated with increased neural activity in hippocampus and amygdala as indexed by p-ERK and c-fos immunolabelling. In vivo electrophysiological recordings of local field potentials (LFPs) showed that 50% reinforcement was associated with increases in the frequency and power of tone-evoked theta oscillations in both the subiculum region of hippocampus and in basolateral amygdala (BLA) during both acquisition (Day 1) and extinction (Day 2) sessions. Tone-evoked LFPs in 50% reinforced animals also showed increases in coherence and bidirectional Granger Causality between hippocampus and amygdala. The results support a Bayesian interpretation of the PREE, in which the phenomenon is driven by increases in the entropy or uncertainty of stimulus contingencies, and indicate a crucial role for hippocampus in mediating this uncertainty-dependent effect. ER -