PMID- 33252329 OWN - NLM STAT- MEDLINE DCOM- 20210401 LR - 20240330 IS - 2050-084X (Electronic) IS - 2050-084X (Linking) VI - 9 DP - 2020 Nov 30 TI - Presynaptic NMDARs cooperate with local spikes toward GABA release from the reciprocal olfactory bulb granule cell spine. LID - 10.7554/eLife.63737 [doi] LID - e63737 AB - In the rodent olfactory bulb the smooth dendrites of the principal glutamatergic mitral cells (MCs) form reciprocal dendrodendritic synapses with large spines on GABAergic granule cells (GC), where unitary release of glutamate can trigger postsynaptic local activation of voltage-gated Na(+)-channels (Na(v)s), that is a spine spike. Can such single MC input evoke reciprocal release? We find that unitary-like activation via two-photon uncaging of glutamate causes GC spines to release GABA both synchronously and asynchronously onto MC dendrites. This release indeed requires activation of Na(v)s and high-voltage-activated Ca(2+)-channels (HVACCs), but also of NMDA receptors (NMDAR). Simulations show temporally overlapping HVACC- and NMDAR-mediated Ca(2+)-currents during the spine spike, and ultrastructural data prove NMDAR presence within the GABAergic presynapse. This cooperative action of presynaptic NMDARs allows to implement synapse-specific, activity-dependent lateral inhibition, and thus could provide an efficient solution to combinatorial percept synthesis in a sensory system with many receptor channels. CI - (c) 2020, Lage-Rupprecht et al. FAU - Lage-Rupprecht, Vanessa AU - Lage-Rupprecht V AD - Neurophysiology, Institute of Zoology, Universitat Regensburg, Regensburg, Germany. AD - Department of Bioinformatics, Fraunhofer SCAI, Sankt Augustin, Germany. FAU - Zhou, Li AU - Zhou L AD - Neurophysiology, Institute of Zoology, Universitat Regensburg, Regensburg, Germany. FAU - Bianchini, Gaia AU - Bianchini G AD - Neurophysiology, Institute of Zoology, Universitat Regensburg, Regensburg, Germany. FAU - Aghvami, S Sara AU - Aghvami SS AD - Neurophysiology, Institute of Zoology, Universitat Regensburg, Regensburg, Germany. AD - School of Electrical and Computer Engineering, University of Tehran, Tehran, Islamic Republic of Iran. AD - School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Islamic Republic of Iran. FAU - Mueller, Max AU - Mueller M AD - Neurophysiology, Institute of Zoology, Universitat Regensburg, Regensburg, Germany. FAU - Rozsa, Balazs AU - Rozsa B AD - Two-Photon Imaging Center, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary. FAU - Sassoe-Pognetto, Marco AU - Sassoe-Pognetto M AD - Neuroscience Department, University of Turin, Torino, Italy. FAU - Egger, Veronica AU - Egger V AUID- ORCID: 0000-0002-5869-8523 AD - Neurophysiology, Institute of Zoology, Universitat Regensburg, Regensburg, Germany. LA - eng SI - Dryad/10.5061/dryad.t4b8gtj04 GR - 01GQ1104/01GQ1502/Bundesministerium fur Bildung und Forschung/International GR - 1479-418.13/German-Israeli Foundation for Scientific Research and Development/International GR - DFG SFB 870/Graduate School of Systemic Neurosciences GSN-LMU/International GR - 682426/ERC_/European Research Council/International GR - GINOP_2.1.1-15-2016-00979/ERC_/European Research Council/International GR - VKSZ_14-1-2015-0155/ERC_/European Research Council/International GR - 712821-NEURAM/ERC_/European Research Council/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201130 PL - England TA - Elife JT - eLife JID - 101579614 RN - 0 (Calcium Channels) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 0 (Sodium Channels) RN - 56-12-2 (gamma-Aminobutyric Acid) SB - IM MH - Action Potentials/physiology MH - Animals MH - Animals, Genetically Modified MH - Calcium Channels MH - Dendritic Cells/*physiology MH - Electric Stimulation MH - Female MH - Gene Expression Regulation MH - Ion Channel Gating MH - Male MH - Neurons/*physiology MH - Olfactory Bulb/*cytology MH - Patch-Clamp Techniques MH - Rats MH - Rats, Wistar MH - Receptors, N-Methyl-D-Aspartate/genetics/*metabolism MH - Sodium Channels MH - gamma-Aminobutyric Acid/genetics/*metabolism PMC - PMC7704106 OTO - NOTNLM OT - granule cell OT - mitral cell OT - neuroscience OT - olfactory bulb OT - presynaptic NMDA receptor OT - rat OT - reciprocal synapse COIS- VL, LZ, GB, SA, MM, MS, VE No competing interests declared, BR BR is a founder of Femtonics Kft and a member of its scientific advisory board. No other competing interests exist. EDAT- 2020/12/01 06:00 MHDA- 2021/04/02 06:00 PMCR- 2020/11/30 CRDT- 2020/11/30 12:09 PHST- 2020/10/05 00:00 [received] PHST- 2020/11/10 00:00 [accepted] PHST- 2020/11/30 12:09 [entrez] PHST- 2020/12/01 06:00 [pubmed] PHST- 2021/04/02 06:00 [medline] PHST- 2020/11/30 00:00 [pmc-release] AID - 63737 [pii] AID - 10.7554/eLife.63737 [doi] PST - epublish SO - Elife. 2020 Nov 30;9:e63737. doi: 10.7554/eLife.63737.