Region-specific involvement of interneuron subpopulations in trauma-related pathology and resilience

Stav Regev-Tsur, Yunus Emre Demiray, Kuldeep Tripathi, Oliver Stork, Gal Richter-Levin, Anne Albrecht

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16 Scopus citations

Abstract

Only a minority of trauma-exposed individuals develops Posttraumatic stress disorder (PTSD) and active processes may support trauma resilience. Individual behavioral profiling allows investigating neurobiological alterations related to resilience or pathology in animal models of PTSD and is utilized here to examine the activation of different interneuron subpopulations of the dentate gyrus-amygdala system associated with trauma resilience or pathology. To model PTSD, rats were exposed to juvenile stress combined with underwater trauma (UWT) in adulthood. Four weeks later, individual anxiety levels were assessed in the elevated plus maze test for classifying rats as highly anxious ‘affected’ vs. ‘non-affected’, i.e. behaving as control animals. Analyzing the activation of specific interneuron subpopulations in the dorsal and ventral dentate gyrus (DG), the basolateral (BLA) and central amygdala by immunohistochemical double-labeling for cFos and different interneuron markers, revealed an increased activation of cholecystokinin (CCK)-positive interneurons in the ventral DG, together with increased activation of parvalbumin- and CCK-positive interneurons in the BLA of affected trauma-exposed rats. By contrast, increased activation of neuropeptide Y (NPY)-positive interneurons was observed in the dorsal DG of trauma-exposed, but non-affected rats. To test for a direct contribution of NPY in the dorsal DG to trauma resilience, a local shRNA-mediated knock down was performed after UWT. Such a treatment significantly reduced the prevalence of resilient animals. Our results suggest that distinct interneuron populations are associated with resilience or pathology in PTSD with high regional specificity. NPY within the dorsal DG was found to significantly contribute to trauma resilience.

Original languageEnglish
Article number104974
JournalNeurobiology of Disease
Volume143
DOIs
StatePublished - Sep 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020 The Author(s)

Funding

This work was supported by funds of the German Research Foundation ( STO488/6 to OS and GRL, CRC779 TPB5 to OS), by The Israeli Science Foundation (grant no. 1517/16 ), and by the Leibniz Postdoctoral Network fellowship (SAW-2015-LIN-3) as well as European fund for regional development (EFRE, grant no: ZS/2016/04/78113 ) to Anne Albrecht.

FundersFunder number
Leibniz Postdoctoral NetworkSAW-2015-LIN-3
Deutsche ForschungsgemeinschaftCRC779 TPB5, STO488/6
Israel Science Foundation1517/16
European Regional Development FundZS/2016/04/78113

    Keywords

    • Behavioral profiling
    • Cholecystokinin
    • Dentate gyrus
    • Interneurons
    • Neuropeptide Y
    • Neuropeptides
    • PTSD
    • Pathology
    • Rat
    • Resilience

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