TY  - JOUR
AU  - Herde, Michel K
AU  - Bohmbach, Kirsten
AU  - Domingos, Cátia
AU  - Vana, Natascha
AU  - Komorowska-Müller, Joanna A
AU  - Passlick, Stefan
AU  - Schwarz, Inna
AU  - Jackson, Colin J
AU  - Dietrich, Dirk
AU  - Schwarz, Martin K
AU  - Henneberger, Christian
TI  - Local Efficacy of Glutamate Uptake Decreases with Synapse Size.
JO  - Cell reports
VL  - 32
IS  - 12
SN  - 2211-1247
CY  - [New York, NY]
PB  - Elsevier
M1  - DZNE-2021-00163
SP  - 108182
PY  - 2020
N1  - ISSN 2211-1247 not unique: **3 hits**.
AB  - Synaptically released glutamate is largely cleared by glutamate transporters localized on perisynaptic astrocyte processes. Therefore, the substantial variability of astrocyte coverage of individual hippocampal synapses implies that the efficacy of local glutamate uptake and thus the spatial fidelity of synaptic transmission is synapse dependent. By visualization of sub-diffraction-limit perisynaptic astrocytic processes and adjacent postsynaptic spines, we show that, relative to their size, small spines display a stronger coverage by astroglial transporters than bigger neighboring spines. Similarly, glutamate transients evoked by synaptic stimulation are more sensitive to pharmacological inhibition of glutamate uptake at smaller spines, whose high-affinity N-methyl-D-aspartate receptors (NMDARs) are better shielded from remotely released glutamate. At small spines, glutamate-induced and NMDAR-dependent Ca2+ entry is also more strongly increased by uptake inhibition. These findings indicate that spine size inversely correlates with the efficacy of local glutamate uptake and thereby likely determines the probability of synaptic crosstalk.
KW  - Amino Acid Transport System X-AG: metabolism
KW  - Animals
KW  - Astrocytes: metabolism
KW  - Calcium: metabolism
KW  - Cell Size
KW  - Dendritic Spines: metabolism
KW  - Female
KW  - Glutamic Acid: metabolism
KW  - Male
KW  - Mice
KW  - Receptors, N-Methyl-D-Aspartate: metabolism
KW  - Synapses: metabolism
KW  - astrocyte morphology (Other)
KW  - astrocytes (Other)
KW  - expansion microscopy (Other)
KW  - glutamate uptake (Other)
KW  - hippocampus (Other)
KW  - multiphoton imaging (Other)
KW  - spine morphology (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:32966786
DO  - DOI:10.1016/j.celrep.2020.108182
UR  - https://pub.dzne.de/record/154309
ER  -