Optical analysis of glutamate spread in the neuropil.

Autor:	Matthews EA; Department of Neurosurgery, University Hospital Bonn, 53127 Bonn, Germany.; Section for Translational Epilepsy Research, Department of Neuropathology, University Hospital Bonn, 53127 Bonn, Germany.; Department of Neurosurgery, Duke University, Durham, NC, USA., Sun W; Department of Neurosurgery, University Hospital Bonn, 53127 Bonn, Germany.; Department of Neuroscience, The Ohio State University, Columbus, OH, USA., McMahon SM; Department of Neurosurgery, University Hospital Bonn, 53127 Bonn, Germany.; Department of Neuroscience, University of Wisconsin, Madison, WI, USA., Doengi M; Institute of Physiology, Medical Faculty, University of Bonn, 53115 Bonn, Germany., Halka L; Institute of Physiology, Medical Faculty, University of Bonn, 53115 Bonn, Germany., Anders S; Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, 53127 Bonn, Germany., Müller JA; Section for Translational Epilepsy Research, Department of Neuropathology, University Hospital Bonn, 53127 Bonn, Germany., Steinlein P; Department of Neurosurgery, University Hospital Bonn, 53127 Bonn, Germany.; Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, Germany., Vana NS; Department of Neurosurgery, University Hospital Bonn, 53127 Bonn, Germany., van Dyk G; Department of Neurosurgery, University Hospital Bonn, 53127 Bonn, Germany., Pitsch J; Section for Translational Epilepsy Research, Department of Neuropathology, University Hospital Bonn, 53127 Bonn, Germany.; Department of Epileptology, University Hospital Bonn, 53127 Bonn, Germany., Becker AJ; Section for Translational Epilepsy Research, Department of Neuropathology, University Hospital Bonn, 53127 Bonn, Germany.; Department of Epileptology, University Hospital Bonn, 53127 Bonn, Germany., Pfeifer A; Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, Germany., Kavalali ET; Department of Pharmacology, The Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37240-7933, USA., Lamprecht A; Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, Germany., Henneberger C; Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, 53127 Bonn, Germany.; German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany.; Institute of Neurology, University College London, London, WC1N 3BG, UK., Stein V; Institute of Physiology, Medical Faculty, University of Bonn, 53115 Bonn, Germany., Schoch S; Section for Translational Epilepsy Research, Department of Neuropathology, University Hospital Bonn, 53127 Bonn, Germany.; Department of Epileptology, University Hospital Bonn, 53127 Bonn, Germany., Dietrich D; Department of Neurosurgery, University Hospital Bonn, 53127 Bonn, Germany.
Jazyk:	angličtina
Zdroj:	Cerebral cortex (New York, N.Y. : 1991) [Cereb Cortex] 2022 Aug 22; Vol. 32 (17), pp. 3669-3689.
DOI:	10.1093/cercor/bhab440
Abstrakt:	Fast synaptic communication uses diffusible transmitters whose spread is limited by uptake mechanisms. However, on the submicron-scale, the distance between two synapses, the extent of glutamate spread has so far remained difficult to measure. Here, we show that quantal glutamate release from individual hippocampal synapses activates extracellular iGluSnFr molecules at a distance of >1.5 μm. 2P-glutamate uncaging near spines further showed that alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-Rs and N-methyl-D-aspartate (NMDA)-Rs respond to distant uncaging spots at approximately 800 and 2000 nm, respectively, when releasing the amount of glutamate contained in approximately five synaptic vesicles. The uncaging-induced remote activation of AMPA-Rs was facilitated by blocking glutamate transporters but only modestly decreased by elevating the recording temperature. When mimicking release from neighboring synapses by three simultaneous uncaging spots in the microenvironment of a spine, AMPA-R-mediated responses increased supra-additively. Interfering with extracellular glutamate diffusion through a glutamate scavenger system weakly reduced field synaptic responses but not the quantal amplitude. Together, our data suggest that the neuropil is more permissive to short-range spread of transmitter than suggested by theory, that multivesicular release could regularly coactivate nearest neighbor synapses and that on this scale glutamate buffering by transporters primarily limits the spread of transmitter and allows for cooperative glutamate signaling in extracellular microdomains. (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)
Databáze:	MEDLINE
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