015 – The neuronal IL-1 receptor is necessary and sufficient for stress-induced social withdrawal and working memory deficits

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015 – The neuronal IL-1 receptor is necessary and sufficient for stress-induced social withdrawal and working memory deficits

Damon DiSabato (1) – Danny Nemeth (2) – Xiaoyu Liu (2) – Kristina Witcher (1) – Braedan Oliver (1) – Jonathan Godbout (1) – Ning Quan (2)
Institute for Behavioral Medicine Research, The Ohio State University, Columbus, United States (1) – Brain Institute, Florida Atlantic University, Jupiter, United States (2)


Stress is a well-known cause of mood disorders such as anxiety, the most prevalent psychiatric disorder affecting upwards of a third of the population. Microglia produce increased levels of pro-inflammatory cytokines such as interleukin-1 beta (IL-1) upon exposure to chronic stress. Our model is paired fighting (PF), a form of social stress in which mice are exposed one-on-one to an aggressor mouse for one hour per day for six days. To dissect the role of IL-1 in such a stress model we developed a genetic tool, the IL-1 receptor restore (IL-1R1r/r) mouse. This allows for globally knocking out IL-1R1 expression and restricting restoration via cell type-specific Cre. IL-1R1 floxed mice (IL-1R1f/f) conversely remove IL-1R1 on specific cell types. Our objectives were (1) to determine effects of PF on peripheral and central IL-1R1 responses, and (2) to identify if neuron-specific IL-1R1 was capable of eliciting anxiety-like behavior. We show that PF caused IL-1R1-dependent social withdrawal, working memory deficits, microglial reactivity, and increased brain cytokines. Cre-mediated neuronal-specific IL-1R1 knockout prevented behavioral effects, indicating its necessity for PF-induced behavior. Conversely, IL-1R1 restored solely on glutamatergic neurons reproduced behaviors from PF in wild-type mice. These data indicate IL-1R1 expression is critical for the behavioral deficits seen after social stress, and that glutamatergic neuronal IL-1R1 is both necessary and sufficient for these effects.