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Kos, A.* ; Lopez, J.P.* ; Bordes, J.* ; De Donno, C. ; Dine, J.* ; Brivio, E.* ; Karamihalev, S.* ; Luecken, M. ; Almeida-Correa, S.* ; Gasperoni, S.* ; Dick, A.* ; Miranda, L.* ; Büttner, M. ; Stoffel, R.* ; Flachskamm, C.* ; Theis, F.J. ; Schmidt, M.V.* ; Chen, A.*

Early life adversity shapes social subordination and cell type-specific transcriptomic patterning in the ventral hippocampus.

Sci. Adv. 9:eadj3793 (2023)

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Adverse events in early life can modulate the response to additional stressors later in life and increase the risk of developing psychiatric disorders. The underlying molecular mechanisms responsible for these effects remain unclear. Here, we uncover that early life adversity (ELA) in mice leads to social subordination. Using single-cell RNA sequencing (scRNA-seq), we identified cell type-specific changes in the transcriptional state of glutamatergic and GABAergic neurons in the ventral hippocampus of ELA mice after exposure to acute social stress in adulthood. These findings were reflected by an alteration in excitatory and inhibitory synaptic transmission induced by ELA in response to acute social stress. Finally, enhancing the inhibitory network function through transient diazepam treatment during an early developmental sensitive period reversed the ELA-induced social subordination. Collectively, this study significantly advances our understanding of the molecular, physiological, and behavioral alterations induced by ELA, uncovering a previously unknown cell type-specific vulnerability to ELA.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Adult Neurogenesis; Stress; Expression; Abuse; Exposure; Amygdala; Model; Brain; Consequences; Persistence

ISSN (print) / ISBN 2375-2548

e-ISSN 2375-2548

Journal Science Advances

Quellenangaben Volume: 9, Issue: 48, Article Number: eadj3793

Publisher American Association for the Advancement of Science (AAAS)

Publishing Place Washington, DC [u.a.]

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Computational Biology (ICB)
Lung Health and Immunity (LHI)

Grants Adelis Foundation
Perlman Family Foundation
Bruno and Simone Licht
Ruhman Family Laboratory for Research on the Neurobiology of Stress
European Union
Canadian Biomarker Integration Network in Depression(CAN-BIND)
Alexandervon Humboldt Foundation
European Molecular Biology Organization