AI Article Synopsis
- IL-6's role in stress-induced synaptic changes is not well understood, prompting researchers to use a genetically modified mouse model to explore how blocking IL-6 trans-signaling affects synaptic function in social defeat scenarios.
- The study found that social defeat altered synaptic properties in the medial prefrontal cortex (mPFC), differentiating between stress-sensitive and stress-resilient mice, highlighting the involvement of IL-6 in these changes.
- Results indicated that IL-6 is essential in mediating synaptic plasticity that influences whether individuals respond with stress resilience or sensitivity following social defeat, supporting the link between synaptic alterations and behavioral outcomes.
Article Abstract
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 (I/I), while S WT animals (but not TG) showed a reduced ratio between AMPA and γ-amino-butyric acid receptor type A (GABAR)-dependent currents (I/I). 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 I/I and eEPSC frequency and negatively with I/I. 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.
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| http://dx.doi.org/10.1016/j.neuroscience.2019.07.002 | DOI Listing |
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