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Many aspects of immunometabolism have been revealed through studies of peripheral immune cells. However, immunometabolic reprogramming of microglia, the resident immune cell of the central nervous system, and the consequential outcome on neuronal activity have remained difficult to unravel. Microglia are highly sensitive to subtle changes in their environment, limiting the techniques available to study their metabolic and inflammatory profiles. Here, using fluorescence lifetime imaging of endogenous NAD(P)H, we measure the metabolic activity of individual microglia within acute hippocampal slices. We observed an LPS\u2010induced increase in aerobic glycolysis, which was blocked by the addition of 5\u2009mM 2\u2010deoxyglucose (2DG). This LPS\u2010induced glycolysis in microglia was necessary for the stabilization of hypoxia inducible factor\u20101\u03b1 (HIF\u20101\u03b1) and production of the proinflammatory cytokine, interleukin\u20101\u03b2 (IL\u20101\u03b2). Upon release, IL\u20101\u03b2 acted via the neuronal interleukin\u20101 receptor to inhibit the formation of synaptic long\u2010term potentiation (LTP) following high frequency stimulation. Remarkably, the addition of 2DG to blunt the microglial glycolytic increase also inhibited HIF\u20101\u03b1 accumulation and IL\u20101\u03b2 production, and therefore rescued LTP in LPS\u2010stimulated slices. Overall, these data reveal the importance of metabolic reprogramming in regulating microglial immune functions, with appreciable outcomes on cytokine release and neuronal activity.<\/jats:p>","DOI":"10.1002\/glia.23913","type":"journal-article","created":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T11:04:24Z","timestamp":1600427064000},"page":"567-578","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["Neuroinflammatory inhibition of synaptic long\u2010term potentiation requires immunometabolic reprogramming of microglia"],"prefix":"10.1002","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8479-5231","authenticated-orcid":false,"given":"Elisa M.","family":"York","sequence":"first","affiliation":[{"name":"Djavad Mowafaghian Centre for Brain Health, Department of Psychiatry University of British Columbia  Vancouver British Columbia Canada"},{"name":"Harvard Medical School Department of Neurobiology  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingfei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Djavad Mowafaghian Centre for Brain Health, Department of Psychiatry University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun B.","family":"Choi","sequence":"additional","affiliation":[{"name":"Djavad Mowafaghian Centre for Brain Health, Department of Psychiatry University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4596-4623","authenticated-orcid":false,"given":"Brian A.","family":"MacVicar","sequence":"additional","affiliation":[{"name":"Djavad Mowafaghian Centre for Brain Health, Department of Psychiatry University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.10.008"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.06.005"},{"issue":"1","key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/0006-8993(93)90959-Q","article-title":"Interleukin 1\u03b2 inhibits synaptic strength and long\u2010term potentiation in the rat CA1 hippocampus","volume":"628","author":"Bellinger F. 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