Neuroinflammation, Neuronal IL-1R1, and Behavior

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Project Summary Neuroinflammation is a significant contributor to most CNS disorders including neurodegenerative diseases and psychological disorders. A hallmark of neuroinflammation is the increased expression of the proinflammatory cytokine interleukin-1 (IL-1) in the brain. How IL-1 causes neuro- and psycho- pathologies is poorly understood. We have recently discovered that the receptor for IL-1, IL-1R1, is expressed in specific sets of neurons in the brain. These neuronal IL-1R1s, nIL-1R1, modulate neuronal activity via non-canonical signaling pathways to alter neuronal function and circuit connectivity. This application is designed to: 1) map nIL-1R1 distribution in the brain, 2)demonstrate the involvement of nIL-1R1 in neuroinflammation induced behavioral deficits and neuropathology, and 3) elucidate the mechanisms of nIL-1R1 mediated neuromodulation.