Local Efficacy of Glutamate Uptake Decreases with Synapse Size
Michel K. Herde,
Kirsten Bohmbach,
Cátia Domingos,
Natascha Vana,
Joanna A. Komorowska-Müller,
Stefan Passlick,
Inna Schwarz,
Colin J. Jackson,
Dirk Dietrich,
Martin K. Schwarz,
Christian Henneberger
Affiliations
Michel K. Herde
Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, Germany
Kirsten Bohmbach
Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, Germany
Cátia Domingos
Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, Germany
Natascha Vana
Department for Neurosurgery, University Hospital Bonn, Bonn, Germany
Joanna A. Komorowska-Müller
Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, Germany
Stefan Passlick
Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, Germany
Inna Schwarz
Institute of Epileptology, Medical Faculty, University of Bonn, Bonn, Germany
Colin J. Jackson
Research School of Chemistry, Australian National University, Canberra, Australia
Dirk Dietrich
Department for Neurosurgery, University Hospital Bonn, Bonn, Germany
Martin K. Schwarz
Institute of Epileptology, Medical Faculty, University of Bonn, Bonn, Germany
Christian Henneberger
Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, Germany; Institute of Neurology, University College London, London, UK; German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany; Corresponding author
Summary: 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.
