Interleukin 6 Dependent Synaptic Plasticity in a Social Defeat-Susceptible Prefrontal Cortex Circuit
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The 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. © 2019 Elsevier Ltd
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GABA; IL-6; NMDA/AMPA ratio; Social defeat; stress; synaptic inhibition/excitation ratio 4 aminobutyric acid receptor; interleukin 6; n methyl dextro aspartic acid receptor; interleukin 6; action potential; animal experiment; animal tissue; Article; brain electrophysiology; controlled study; excitatory postsynaptic potential; forced swim test; male; medial prefrontal cortex; mouse; nerve cell plasticity; nonhuman; priority journal; protein function; signal transduction; social stress; whole cell patch clamp; animal; genetics; metabolism; nerve cell network; nerve cell plasticity; patch clamp technique; physiology; prefrontal cortex; social dominance; transgenic mouse; Action Potentials; Animals; Excitatory Postsynaptic Potentials; Interleukin-6; Male; Mice; Mice, Transgenic; Nerve Net; Neuronal Plasticity; Patch-Clamp Techniques; Prefrontal Cortex; Social Dominance
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