Aberrant hippocampal Ca 2+ micro-waves following synapsin-dependent adeno-associated viral expression of Ca 2+ indicators
Year: 2023
Type: preprint
Abstract: 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. Impact statement: Common AAV transduction procedures induce artefactual spatially confined Ca 2+ waves in the hippocampus.
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Deutsche Forschungsgemeinschaft, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Institutes of Health, Office of Naval Research, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, HORIZON EUROPE European Research Council
Awards: G1402406509, G1480873338, G195628441, G2941508635, Spinning disk confocal microscope, Inter-areal Neocortical Dynamics during Mouse Behaviour, The Neglected Subiculum: Decoding and Manipulating Memory Retrieval with Multiphoton Holography, NSF-ANR: REBIRTH: Understanding The Self-Assembly Of The Nervous System of Hydra Vulgaris, Neural Processing of Distinct Prediction Errors: Theory, Mechanisms & Interventions, G645767916, An auditory virtual environment to control and study the feedback loops of neuronal learning, Targeting epilepsy with phototherapeutics, Effect of GABAergic inhibition of dendritic spines on synaptic pruning in the medial prefrontal cortex during adolescence, Reexamining the Role of Dendrites in Neuronal Function
OpenAlex ID: W4388603642