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However, the data supporting this view come largely from work in synaptosomes, which may overrepresent nerve-terminal uptake over astrocytic uptake. Here, we quantify real-time glutamate dynamics in HD mouse models by high-speed imaging of an intensity-based glutamate-sensing fluorescent reporter (iGluSnFR) and electrophysiological recordings of synaptically activated transporter currents in astrocytes. These techniques reveal a disconnect between the results obtained in synaptosomes and those <jats:italic>in situ<\/jats:italic>. Exogenous glutamate uptake is impaired in synaptosomes, whereas real-time measures of glutamate clearance in the HD striatum are normal or even accelerated, particularly in the aggressive <jats:italic>R6\/2<\/jats:italic> model. Our results highlight the importance of quantifying glutamate dynamics under endogenous release conditions, and suggest that the widely cited uptake impairment in HD does not contribute to pathogenesis.<\/jats:p>","DOI":"10.1038\/ncomms11251","type":"journal-article","created":{"date-parts":[[2016,4,7]],"date-time":"2016-04-07T09:11:35Z","timestamp":1460020295000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":103,"title":["Real-time imaging of glutamate clearance reveals normal striatal uptake in Huntington disease mouse models"],"prefix":"10.1038","volume":"7","author":[{"given":"Matthew P.","family":"Parsons","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu P.","family":"Vanni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron L.","family":"Woodard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rujun","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy H.","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn A.","family":"Raymond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,4,7]]},"reference":[{"key":"BFncomms11251_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0301-0082(00)00067-8","volume":"65","author":"NC Danbolt","year":"2001","unstructured":"Danbolt, N. 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