Single Synapse Indicators of Impaired Glutamate Clearance Derived from Fast iGlu u Imaging of Cortical Afferents in the Striatum of Normal and Huntington (Q175) Mice

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Anton DvorzhakRosemarie Grantyn

Abstract

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 u We report findings from individual corticostriatal synapses in acute slices prepared from mice of either sex that were >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 u 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 u amplitude, as an indicator of release, were prolonged and reduced, respectively. Treatment of WT preparations with the astr...Continue Reading

Citations

Apr 18, 2020·PLoS Computational Biology·Adam PonziJames Kozloski
May 20, 2020·Scientific Reports·Matthew J BroadheadGareth B Miles
Nov 18, 2020·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Carlos Cepeda, Michael S Levine
Dec 4, 2019·Biophysical Journal·Catherine CoatesKatalin Török
Feb 23, 2021·Journal of Neuroscience Research·Kyle J BrymerMatthew P Parsons
Apr 13, 2021·Frontiers in Cellular Neuroscience·Crystal M WilkieMatthew P Parsons

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