A neural substrate for resistance to change in the ventral hippocampus

Abstract

Strong prior beliefs can render individuals resistant to change, even when outcomes contradict expectations, yet the neural mechanisms supporting such stability remain poorly understood. Here we show that the ventral hippocampus (vCA1) actively stabilizes inferred contextual state (belief) during aversive memory extinction in a behavior-dependent manner. Using in vivo calcium imaging, we identify a subset of vCA1 neurons that exhibit selective reductions in activity when expected aversive outcomes do not occur during extinction. Axonal calcium imaging further reveals that reduced signals are broadcast to basal amygdala, nucleus accumbens, and medial prefrontal cortex. Optogenetic manipulations demonstrate that these signals actively suppress extinction learning and promote persistence of defensive response. Computational modeling indicates that vCA1 omission-related signals reflect discrepancies between beliefs and observed omission of the expected outcome, thereby maintaining the aversive belief. Crucially, convergent evidence from calcium imaging, modelling, and closed-loop optogenetic manipulations reveals that vCA1 omission-related signals are specific to the period during which animals execute defensive behavior driven by their inferred aversive state. These findings identify a novel mechanism in vCA1 that stabilizes inferred aversive state despite changes in stimulus contingencies and suggest a key role of vCA1 in belief-based control of learning.