PMID- 37986838
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240210
DP  - 2024 Jan 30
TI  - Aberrant hippocampal Ca(2+) micro-waves following synapsin-dependent 
      adeno-associated viral expression of Ca(2+) indicators.
LID - 2023.11.08.566169 [pii]
LID - 10.1101/2023.11.08.566169 [doi]
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 Ca(2+) 
      micro-waves 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. Ca(2+) micro-waves developed in 
      hippocampal CA1 and CA3, but not dentate gyrus (DG) nor neocortex, were typically 
      first observed at 4 weeks after viral transduction, and persisted up to at least 
      8 weeks. The phenomenon was robust, observed across laboratories with various 
      experimenters and setups. Our results indicate that aberrant hippocampal Ca(2+) 
      micro-waves 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 artifact. The results show that 
      commonly used Ca(2+)-indicator AAV transduction procedures can produce 
      artefactual Ca(2+) responses. Our aim is to raise awareness in the field of these 
      artefactual transduction-induced Ca(2+) micro-waves and we provide a potential 
      solution.
FAU - Masala, Nicola
AU  - Masala N
AD  - University of Bonn, Faculty of Medicine, Institute for Experimental Epileptology 
      and Cognition Research (IEECR), Bonn, Germany.
AD  - University Hospital Bonn.
AD  - Department of Epileptology, University Hospital Bonn, Bonn, Germany.
FAU - Mittag, Manuel
AU  - Mittag M
AD  - Neuroimmunology and Imaging Group, German Center for Neurodegenerative Diseases 
      (DZNE), Bonn, Germany.
FAU - Giovannetti, Eleonora Ambrad
AU  - Giovannetti EA
AD  - Neuroimmunology and Imaging Group, German Center for Neurodegenerative Diseases 
      (DZNE), Bonn, Germany.
FAU - O'Neil, Darik A
AU  - O'Neil DA
AD  - NeuroTechnology Center, Columbia University, New York, NY, USA.
FAU - Distler, Fabian
AU  - Distler F
AD  - University of Bonn, Faculty of Medicine, Institute for Experimental Epileptology 
      and Cognition Research (IEECR), Bonn, Germany.
AD  - University Hospital Bonn.
FAU - Rupprecht, Peter
AU  - Rupprecht P
AD  - Brain Research Institute, University of Zurich, Zurich, Switzerland.
AD  - Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland.
FAU - Helmchen, Fritjof
AU  - Helmchen F
AUID- ORCID: 0000-0002-8867-9569
AD  - Brain Research Institute, University of Zurich, Zurich, Switzerland.
AD  - Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland.
FAU - Yuste, Rafael
AU  - Yuste R
AD  - NeuroTechnology Center, Columbia University, New York, NY, USA.
FAU - Fuhrmann, Martin
AU  - Fuhrmann M
AD  - Neuroimmunology and Imaging Group, German Center for Neurodegenerative Diseases 
      (DZNE), Bonn, Germany.
FAU - Beck, Heinz
AU  - Beck H
AD  - University of Bonn, Faculty of Medicine, Institute for Experimental Epileptology 
      and Cognition Research (IEECR), Bonn, Germany.
AD  - University Hospital Bonn.
AD  - German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
FAU - Wenzel, Michael
AU  - Wenzel M
AD  - University of Bonn, Faculty of Medicine, Institute for Experimental Epileptology 
      and Cognition Research (IEECR), Bonn, Germany.
AD  - University Hospital Bonn.
AD  - Department of Epileptology, University Hospital Bonn, Bonn, Germany.
FAU - Kelly, Tony
AU  - Kelly T
AUID- ORCID: 0000-0001-6066-0455
AD  - University of Bonn, Faculty of Medicine, Institute for Experimental Epileptology 
      and Cognition Research (IEECR), Bonn, Germany.
AD  - University Hospital Bonn.
LA  - eng
GR  - F99 NS134209/NS/NINDS NIH HHS/United States
GR  - R01 MH115900/MH/NIMH NIH HHS/United States
GR  - RM1 NS132981/NS/NINDS NIH HHS/United States
PT  - Preprint
DEP - 20240130
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
PMC - PMC10659308
COIS- Conflict of Interest None of the authors have a conflict of interest.
EDAT- 2023/11/21 06:42
MHDA- 2023/11/21 06:43
PMCR- 2024/02/01
CRDT- 2023/11/21 05:07
PHST- 2023/11/21 06:42 [pubmed]
PHST- 2023/11/21 06:43 [medline]
PHST- 2023/11/21 05:07 [entrez]
PHST- 2024/02/01 00:00 [pmc-release]
AID - 2023.11.08.566169 [pii]
AID - 10.1101/2023.11.08.566169 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2024 Jan 30:2023.11.08.566169. doi: 
      10.1101/2023.11.08.566169.