{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T12:51:45Z","timestamp":1791031905499,"version":"4.1.0"},"reference-count":52,"publisher":"Society for Neuroscience","issue":"31","license":[{"start":{"date-parts":[[2012,2,3]],"date-time":"2012-02-03T00:00:00Z","timestamp":1328227200000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2011,8,3]]},"abstract":"<jats:p>\n                    The concentration of amyloid-\u03b2 (A\u03b2) within the brain extracellular space is one determinant of whether the peptide will aggregate into toxic species that are important in Alzheimer's disease (AD) pathogenesis. Some types of synaptic activity can regulate A\u03b2 levels. Here we demonstrate two distinct mechanisms that are simultaneously activated by NMDA receptors and regulate brain interstitial fluid (ISF) A\u03b2 levels in opposite directions in the living mouse. Depending on the dose of NMDA administered locally to the brain, ISF A\u03b2 levels either increase or decrease. Low doses of NMDA increase action potentials and synaptic transmission which leads to an elevation in synaptic A\u03b2 generation. In contrast, high doses of NMDA activate signaling pathways that lead to ERK (extracellular-regulated kinase) activation, which reduces processing of APP into A\u03b2. This depression in A\u03b2 via APP processing occurs despite dramatically elevated synaptic activity. Both of these synaptic mechanisms are simultaneously active, with the balance between them determining whether ISF A\u03b2 levels will increase or decrease. NMDA receptor antagonists increase ISF A\u03b2 levels, suggesting that basal activity at these receptors normally suppresses A\u03b2 levels\n                    <jats:italic>in vivo<\/jats:italic>\n                    . This has implications for understanding normal A\u03b2 metabolism as well as AD pathogenesis.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.0607-11.2011","type":"journal-article","created":{"date-parts":[[2011,8,3]],"date-time":"2011-08-03T19:48:44Z","timestamp":1312400924000},"page":"11328-11337","source":"Crossref","is-referenced-by-count":68,"title":["Opposing Synaptic Regulation of Amyloid-\u03b2 Metabolism by NMDA Receptors\n                    <i>In Vivo<\/i>"],"prefix":"10.1523","volume":"31","author":[{"given":"Deborah K.","family":"Verges","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L.","family":"Restivo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Whitney D.","family":"Goebel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David 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