A sensitivity-consistency trade-off in memory formation regulated by dentate gyrus inhibition

Abstract

A core computational challenge for memory systems is the need to balance two opposing demands: (1) sensitivity to subtle input differences for flexible encoding, and (2) consistency to preserve stable, interference-resistant representations. How the brain dynamically regulates this trade-off remains unclear. Here, we show that modulating parvalbumin-expressing (PV+) interneurons in the dentate gyrus regulates this balance by shifting hippocampal computation between sensitivity and consistency regimes. Combining cell-type-specific pharmacogenetics, behavioral assays, and computational modeling, we found that reducing PV+-mediated inhibition during encoding enhanced the subsequent discrimination of similar inputs but it increased vulnerability to interference. In contrast, increased inhibition stabilized memory representations at the cost of discriminability. Together, the results establish PV+ interneurons as key modulators of hippocampal memory processing, enabling the system to prioritize either flexible updating or robust retention based on inhibitory tone at the time of encoding. This sensitivity-consistency continuum may reflect a fundamental organizing principle of memory computation.