TY  - JOUR
AU  - Masala, Nicola
AU  - Mittag, Manuel
AU  - Ambrad Giovannetti, Eleonora
AU  - O'Neil, Darik A
AU  - Distler, Fabian J
AU  - Rupprecht, Peter
AU  - Helmchen, Fritjof
AU  - Yuste, Rafael
AU  - Fuhrmann, Martin
AU  - Beck, Heinz
AU  - Wenzel, Michael
AU  - Kelly, Tony
TI  - Aberrant hippocampal Ca2+ microwaves following synapsin-dependent adeno-associated viral expression of Ca2+ indicators.
JO  - eLife
VL  - 13
SN  - 2050-084X
CY  - Cambridge
PB  - eLife Sciences Publications
M1  - DZNE-2024-00921
SP  - RP93804
PY  - 2024
AB  - Genetically encoded calcium indicators (GECIs) such as GCaMP are invaluable tools in neuroscience to monitor neuronal activity using optical imaging. The viral transduction of GECIs is commonly used to target expression to specific brain regions, can be conveniently used with any mouse strain of interest without the need for prior crossing with a GECI mouse line, and avoids potential hazards due to the chronic expression of GECIs during development. A key requirement for monitoring neuronal activity with an indicator is that the indicator itself minimally affects activity. Here, using common adeno-associated viral (AAV) transduction procedures, we describe spatially confined aberrant Ca2+ microwaves slowly travelling through the hippocampus following expression of GCaMP6, GCaMP7, or R-CaMP1.07 driven by the synapsin promoter with AAV-dependent gene transfer in a titre-dependent fashion. Ca2+ microwaves developed in hippocampal CA1 and CA3, but not dentate gyrus nor neocortex, were typically first observed at 4 wk after viral transduction, and persisted up to at least 8 wk. The phenomenon was robust and observed across laboratories with various experimenters and setups. Our results indicate that aberrant hippocampal Ca2+ microwaves depend on the promoter and viral titre of the GECI, density of expression, as well as the targeted brain region. We used an alternative viral transduction method of GCaMP which avoids this artefact. The results show that commonly used Ca2+-indicator AAV transduction procedures can produce artefactual Ca2+ responses. Our aim is to raise awareness in the field of these artefactual transduction-induced Ca2+ microwaves, and we provide a potential solution.
KW  - Animals
KW  - Dependovirus: genetics
KW  - Synapsins: metabolism
KW  - Synapsins: genetics
KW  - Calcium: metabolism
KW  - Hippocampus: metabolism
KW  - Mice
KW  - Genetic Vectors
KW  - Transduction, Genetic
KW  - Promoter Regions, Genetic
KW  - Mice, Inbred C57BL
KW  - Male
KW  - AAV (Other)
KW  - GCaMP (Other)
KW  - GECI (Other)
KW  - in vivo (Other)
KW  - mouse (Other)
KW  - neuroscience (Other)
KW  - Synapsins (NLM Chemicals)
KW  - Calcium (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39042440
C2  - pmc:PMC11265795
DO  - DOI:10.7554/eLife.93804
UR  - https://pub.dzne.de/record/270888
ER  -