Thy1-YFP-H mice (stock 003782)57 (link), which express yellow fluorescent protein (YFP) in L5 pyramidal neurons, Rosa26-stop-DTR mice (stock 007900)58 (link), which express a conditional DTR-encoding allele in the ROSA locus, Rag1−/− mice (stock 002216)59 (link), Tnf−/− mice (stock 005540)60 (link), Il6−/− mice (stock 002650) and B6 CD45.1 mice (stock 002014) were purchased from the Jackson Laboratory. Cx3cr1CreER mice35 (link) were obtained from the laboratory of Wen-Biao Gan (New York University). Cx3cr1GFP mice34 (link) were obtained from the laboratory of Dan Littman (New York University). To image dendritic spine plasticity in Cx3cr1CreER/+;R26iDTR/+ and Tnf−/− mice, these mice were crossed to Thy1-YFP-H mice. For systemic immune challenge, mice were administered poly(I:C) (Sigma P1530; by i.p. injection) that was dissolved in DPBS. Mice were group-housed in temperature-controlled rooms on a 12-h light–dark cycle and were randomly assigned to different treatment groups. The group size was determined based on previous studies using the same methodologies28 (link),29 (link),30 (link),31 (link),32 (link). Both male and female mice were used. All mice were maintained at the NYU Skirball Institute specific-pathogen-free animal facility and handled in accordance with the institutional guidelines for animal care and use.