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Significance Priming with classic lymphocyte cytokine, interferon-gamma (IFN-γ) is crucial during the complex activation process of tissue macrophages, such as microglia in the CNS, under pathological conditions. According to current biological concepts, priming permits an exaggerated macrophage immune response given a secondary inflammatory stimulus like bacterial components occurs. Here, we demonstrate that priming with IFN-γ itself induces proliferation and moderate activation of microglia, including up-regulation of inducible nitric oxide synthase (iNOS). Importantly, the concomitant moderate release of nitric oxide (NO) is sufficient to disturb fast neuronal network oscillations (30–70 Hz) that underlie higher brain functions, such as perception, attention, and memory. This mechanism might contribute to early cognitive impairment in chronic brain disorders, such as multiple sclerosis and Alzheimer’s disease.

Priming of microglia with IFN-γ slows neuronal gamma oscillations in situ