• Neuroscience · Aug 2019

    Interleukin 6 Dependent Synaptic Plasticity in a Social Defeat-Susceptible Prefrontal Cortex Circuit.

    • Eric Esquivel-Rendón, Jorge Vargas-Mireles, Roberto Cuevas-Olguín, Marcela Miranda-Morales, Palmira Acosta-Mares, Francisco García-Oscos, Juan Carlos Pineda, Humberto Salgado, Stefan Rose-John, and Marco Atzori.
    • Universidad Autónoma de San Luis Potosí, Facultad de Ciencias, San Luis Potosí, San Luis Potosí, Mexico.
    • Neuroscience. 2019 Aug 21; 414: 280-296.

    AbstractThe role of the pro-inflammatory cytokine interleukin-6 (IL-6) in the etiology of stress-induced synaptic plasticity is yet unknown. We took advantage of a genetically modified mouse (TG) in which IL-6 trans-signaling via the soluble IL-6 receptor was blocked, to determine the role of IL-6 trans-signaling in the effects of a Social Defeat protocol (SD) on synaptic function of the medial prefrontal cortex (mPFC). Synaptic function in stress-sensitive (S) and stress-resilient (R) animals was studied in a mPFC slice preparation with whole-cell patch-clamp recording. SD altered numerous synaptic properties of the mPFC: R WT (but not TG) displayed a decreased ratio between N methyl-D-aspartate receptor (NMDAR-) dependent and amino propionic acid receptor (AMPAR-) dependent-current (INMDA/IAMPA), while S WT animals (but not TG) showed a reduced ratio between AMPA and γ-amino-butyric acid receptor type A (GABAAR)-dependent currents (IAMPA/IGABA). Also, SD induced an increase in the frequency but a decrease in the amplitude of excitatory action-potential dependent PSCs (sEPSCs), both in an IL-6 dependent manner, as well as a generalized (S/R-independent) decrease in the frequency of action potential independent (miniature) excitatory (IL-6 dependent) as well as inhibitory (IL-6 independent) postsynaptic current frequency. Interestingly, corner preference (measuring the intensity of social defeat) correlated positively with INMDA/IAMPA and eEPSC frequency and negatively with IAMPA/IGABA. Our results suggest that SD induces behaviorally-relevant synaptic rearrangement in mPFC circuits, part of which is IL-6 dependent. In particular, IL-6 is necessary to produce synaptic plasticity leading to stress resilience in some individuals, but to stress sensitivity in others.Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

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