Hippocampal sharp wave ripples underlie stress susceptibility in male mice

Nahoko Kuga, Ryota Nakayama, Shota Morikawa, Haruya Yagishita, Daichi Konno, Hiromi Shiozaki, Natsumi Honjoya, Yuji Ikegaya and Takuya Sasaki ()
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Nahoko Kuga: The University of Tokyo
Ryota Nakayama: The University of Tokyo
Shota Morikawa: The University of Tokyo
Haruya Yagishita: The University of Tokyo
Daichi Konno: The University of Tokyo
Hiromi Shiozaki: Tohoku University
Natsumi Honjoya: Tohoku University
Yuji Ikegaya: The University of Tokyo
Takuya Sasaki: The University of Tokyo

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract The ventral hippocampus (vHC) is a core brain region for emotional memory. Here, we examined how the vHC regulates stress susceptibility from the level of gene expression to neuronal population dynamics in male mice. Transcriptome analysis of samples from stress-naïve mice revealed that intrinsic calbindin (Calb1) expression in the vHC is associated with susceptibility to social defeat 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. Poststress vHC SWRs triggered synchronous reactivation of stress memory-encoding neuronal ensembles and facilitated information transfer to the amygdala. Suppression of poststress vHC 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 ventral hippocampal SWRs serves as a crucial neurophysiological substrate for determining stress susceptibility.

Date: 2023
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DOI: 10.1038/s41467-023-37736-x

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