PMID- 29935099 OWN - NLM STAT- MEDLINE DCOM- 20190910 LR - 20210109 IS - 1098-2396 (Electronic) IS - 0887-4476 (Print) IS - 0887-4476 (Linking) VI - 72 IP - 12 DP - 2018 Dec TI - Presynaptic GCaMP expression decreases vesicle release probability at the calyx of Held. PG - e22040 LID - 10.1002/syn.22040 [doi] LID - e22040 AB - Synaptic vesicle (SV) exocytosis is intimately dependent on free local Ca(2+) near active zones. Genetically encoded calcium indicators (GECIs) have become an indispensable tool to monitor calcium dynamics during physiological responses, and they are widely used as a proxy to monitor activity in neuronal ensembles and at synaptic terminals. However, GECIs' ability to bind Ca(2+) at physiologically relevant concentration makes them strong candidates to affect calcium homeostasis and alter synaptic transmission by exogenously increasing Ca(2+) buffering. In the present study, we show that genetically expressed GCaMP6m modulates SV release probability at the mouse calyx of Held synapse. GCaMP6m expression for approximately three weeks decreased initial SV release for both low-frequency stimulation and high-frequency stimulation trains, and slowed presynaptic short-term depression. However, GCaMP6m does not affect quantal events during spontaneous activity at this synapse. This study emphasizes the careful use of GECIs as monitors of neuronal activity and inspects the role of these transgenic indicators which may alter calcium-dependent physiological responses. CI - (c) 2018 The Authors. Synapse Published by Wiley Periodicals, Inc. FAU - Singh, Mahendra AU - Singh M AD - Department of Physiology and Cell Biology, University of Nevada, Reno, Nevada, 89557. FAU - Lujan, Brendan AU - Lujan B AD - Department of Physiology and Cell Biology, University of Nevada, Reno, Nevada, 89557. AD - Currently at Vollum Institute, Oregon Health and Science University, Portland, Oregon. FAU - Renden, Robert AU - Renden R AUID- ORCID: 0000-0001-7905-4789 AD - Department of Physiology and Cell Biology, University of Nevada, Reno, Nevada, 89557. LA - eng GR - P20 GM103554/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20180717 PL - United States TA - Synapse JT - Synapse (New York, N.Y.) JID - 8806914 RN - 0 (Calcium-Binding Proteins) RN - 0 (Luminescent Proteins) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Calcium/metabolism MH - Calcium-Binding Proteins/genetics/*metabolism MH - *Exocytosis MH - Female MH - Genes, Reporter MH - Luminescent Proteins/genetics/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Presynaptic Terminals/metabolism MH - Synaptic Vesicles/*metabolism PMC - PMC6186185 MID - NIHMS987362 OTO - NOTNLM OT - animals OT - calcium OT - exocytosis OT - mice OT - presynaptic terminals OT - synaptic transmission OT - synaptic vesicles EDAT- 2018/06/24 06:00 MHDA- 2019/09/11 06:00 PMCR- 2018/11/07 CRDT- 2018/06/24 06:00 PHST- 2018/05/03 00:00 [received] PHST- 2018/06/04 00:00 [revised] PHST- 2018/06/05 00:00 [accepted] PHST- 2018/06/24 06:00 [pubmed] PHST- 2019/09/11 06:00 [medline] PHST- 2018/06/24 06:00 [entrez] PHST- 2018/11/07 00:00 [pmc-release] AID - SYN22040 [pii] AID - 10.1002/syn.22040 [doi] PST - ppublish SO - Synapse. 2018 Dec;72(12):e22040. doi: 10.1002/syn.22040. Epub 2018 Jul 17.