{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:52:26Z","timestamp":1792673546112,"version":"4.5.0"},"reference-count":72,"publisher":"Society for Neuroscience","issue":"20","license":[{"start":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T00:00:00Z","timestamp":1573776000000},"content-version":"vor","delay-in-days":260,"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":[[2019,5,15]]},"abstract":"<jats:p>\n                    Changes in the balance between glutamate (Glu) release and uptake may stimulate synaptic reorganization and even synapse loss. In the case of neurodegeneration, a mismatch between astroglial Glu uptake and presynaptic Glu release could be detected if both parameters were assessed independently and at a single-synapse level. This has now become possible due to a new imaging assay with the genetically encoded ultrafast Glu sensor iGlu\n                    <jats:italic>\n                      <jats:sub>u<\/jats:sub>\n                    <\/jats:italic>\n                    . We report findings from individual corticostriatal synapses in acute slices prepared from mice of either sex that were &gt;1 year of age. Contrasting patterns of short-term plasticity and a size criterion identified two classes of terminals, presumably corresponding to the previously defined IT (intratelencephalic) and PT (pyramidal tract) synapses. The latter exhibited a higher degree of frequency potentiation\/residual Glu accumulation and were selected for our first iGlu\n                    <jats:italic>\n                      <jats:sub>u<\/jats:sub>\n                    <\/jats:italic>\n                    single-synapse study in Q175 mice, a model of Huntington's disease (HD). In HD mice, the decay time constant of the perisynaptic Glu concentration (TauD), as an indicator of uptake, and the peak iGlu\n                    <jats:italic>\n                      <jats:sub>u<\/jats:sub>\n                    <\/jats:italic>\n                    amplitude, as an indicator of release, were prolonged and reduced, respectively. Treatment of WT preparations with the astrocytic Glu uptake blocker TFB-TBOA (100 n\n                    <jats:sc>m<\/jats:sc>\n                    ) mimicked the TauD changes in homozygotes. Considering the largest TauD values encountered in WT, \u223c40% of PT synapses tested in Q175 heterozygotes can be classified as dysfunctional. Moreover, HD but not WT synapses exhibited a positive correlation between TauD and the peak amplitude of iGlu\n                    <jats:italic>\n                      <jats:sub>u<\/jats:sub>\n                    <\/jats:italic>\n                    . Finally, EAAT2 (excitatory amino acid transport protein 2) immunoreactivity was reduced next to corticostriatal terminals. Thus, astrocytic Glu transport remains a promising target for therapeutic intervention.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>\n                    Alterations in astrocytic Glu uptake can play a role in synaptic plasticity and neurodegeneration. Until now, the sensitivity of synaptic responses to pharmacological transport block and the resulting activation of NMDA receptors were regarded as reliable evidence for a mismatch between synaptic uptake and release. But the latter parameters are interdependent. Using a new genetically encoded sensor to monitor extracellular glutamate concentration ([Glu]) at individual corticostriatal synapses, we can now quantify the time constant of perisynaptic [Glu] decay (as an indicator of uptake) and the maximal [Glu] elevation next to the active zone (as an indicator of Glu release). The results provide a positive answer to the hitherto unresolved question of whether neurodegeneration (e.g., Huntington's disease) associates with a glutamate uptake deficit at tripartite excitatory synapses.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.2865-18.2019","type":"journal-article","created":{"date-parts":[[2019,2,28]],"date-time":"2019-02-28T17:44:13Z","timestamp":1551375853000},"page":"3970-3982","source":"Crossref","is-referenced-by-count":30,"title":["Single Synapse Indicators of Impaired Glutamate Clearance Derived from Fast iGlu\n                    <i>\n                      <sub>u<\/sub>\n                    <\/i>\n                    Imaging of Cortical Afferents in the Striatum of Normal and Huntington (Q175) 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