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An updated suite of viral vectors for in vivo calcium imaging using intracerebral and retro-orbital injections in male mice

Sverre Grødem, Ingeborg Nymoen, Guro Helén Vatne, Frederik Sebastian Rogge, Valgerður Björnsdóttir, Kristian Kinden Lensjø, Marianne Fyhn

2023Nature Communications56 citationsDOIOpen Access PDF

Abstract

Abstract Genetically encoded Ca 2+ indicators (GECIs) are widely used to measure neural activity. Here, we explore the use of systemically administered PHP.eB AAVs for brain-wide expression of GECIs and compare the expression properties to intracerebrally injected AAVs in male mice. We show that systemic administration is a promising strategy for imaging neural activity. Next, we establish the use of EE-RR- (soma) and RPL10a (Ribo) soma-targeting peptides with the latest jGCaMP and show that EE-RR-tagged jGCaMP8 gives rise to strong expression but limited soma-targeting. In contrast, Ribo-tagged jGCaMP8 lacks neuropil signal, but the expression rate is reduced. To combat this, we modified the linker region of the Ribo-tag (RiboL1-). RiboL1-jGCaMP8 expresses faster than Ribo-jGCaMP8 but remains too dim for reliable use with systemic virus administration. However, intracerebral injections of the RiboL1-tagged jGCaMP8 constructs provide strong Ca 2+ signals devoid of neuropil contamination, with remarkable labeling density.

Topics & Concepts

In vivoCalcium imagingVirologySuiteCalciumNeuroscienceBiologyComputational biologyMedicineInternal medicineGeneticsGeographyArchaeologyVirus-based gene therapy researchBacteriophages and microbial interactionsRNA Interference and Gene Delivery
An updated suite of viral vectors for in vivo calcium imaging using intracerebral and retro-orbital injections in male mice | Litcius