Abstract
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.
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•Relative astrocytic coverage of glutamatergic spines decreases with spine size•Control of perisynaptic glutamate transients by uptake decreases with spine size•Control of receptor-mediated Ca2+ entry by uptake decreases with spine size•Accordingly, small spines are better shielded from invading glutamate
Herde et al. demonstrate a dependence of the local efficacy of glutamate uptake at glutamatergic synapses on spine size. As predicted by the relative astrocytic coverage of spines, extracellular glutamate transients and Ca2+ entry through glutamate receptors are less strongly controlled by glutamate uptake at large than at small spines.