Parvalbumin-positive neurons in the medial septum participate in the formation of hippocampal-dependent spatial memory

GABAergic medial septal neurons play a key role in regulating hippocampus-dependent spatial memory, but the underlying mechanisms are not yet fully understood. In male mice, we establish an object-place recognition impairment model using an acute sleep deprivation protocol. Here we show that parvalbumin-positive neurons in the medial septum regulate object-location memory specificity during encoding by modulating hippocampal place cell population activity. Using in vivo electrophysiology combined with optogenetics, we characterize the role of medial septal parvalbumin-positive neurons in object-place recognition during memory encoding. Preference for objects relocated to novel positions parallels directional shifts in place fields of remapping neuronal populations, as well as decreased co-activity among place cells in dorsal CA1 during the encoding phase. Activating medial septal parvalbumin-positive neurons during memory encoding rescues object-place recognition impairments. These findings suggest that parvalbumin-positive neurons in the medial septum play a causal role in object-place recognition memory. This study shows that medial septal parvalbumin neurons causally control hippocampal place cell dynamics during memory encoding, thereby supporting object-place recognition and rescuing sleep deprivation-induced memory deficits.