Hippocampal sharp wave ripple-induced memory reactivation underlies stress susceptibility. Mus musculus

The ventral hippocampus (vHC) has been identified as a core brain region in emotional memory. Here, we examined whether and how the vHC regulates stress susceptibility from the level of gene expression to neuronal population dynamics. Transcriptome analysis of samples from stress-naïve mice revealed that intrinsic calbindin (Calb1) expression in the vHC predicts susceptibility to social defeat (SD) stress. Mice with Calb1 gene knockdown in the vHC exhibited increased stress resilience and failed to show the increase in the poststress ventral hippocampal sharp wave ripple (SWR) rate specifically observed in susceptible mice. Poststress ventral hippocampal SWRs triggered synchronous reactivation of stress memory-encoding neuronal ensembles and facilitated information transfer to the amygdala. Suppression of poststress ventral hippocampal SWRs by real-time feedback stimulation or walking prevented social behavior deficits. Taken together, our results demonstrate that internal reactivation of memories of negative stressful episodes supported by Calb1-dependent ventral hippocampal SWRs serves as a crucial neurophysiological substrate for determining stress susceptibility.