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Publication : Optical opening of the blood-brain barrier for targeted and ultra-sparse viral infection of cells in mouse cortex.

First Author  Reeson P Year  2023
Journal  Cell Rep Methods Volume  3
Issue  6 Pages  100489
PubMed ID  37426748 Mgi Jnum  J:338448
Mgi Id  MGI:7512721 Doi  10.1016/j.crmeth.2023.100489
Citation  Reeson P, et al. (2023) Optical opening of the blood-brain barrier for targeted and ultra-sparse viral infection of cells in mouse cortex. Cell Rep Methods 3(6):100489
abstractText  Adeno-associated viruses (AAVs) are used in a wide array of experimental situations for driving expression of biosensors, recombinases, and opto-/chemo-genetic actuators in the brain. However, conventional approaches for minimally invasive, spatially precise, and ultra-sparse AAV-mediated transduction of cells during imaging experiments have remained a significant challenge. Here, we show that intravenous injection of commercially available AAVs at different doses, combined with laser-based perforation of cortical capillaries through a cranial widow, allows for ultra-sparse, titratable, and micron-level precision for delivery of viral vectors with relatively little inflammation or tissue damage. Further, we show the utility of this approach for eliciting sparse expression of GCaMP6, channelrhodopsin, or fluorescent reporters in neurons and astrocytes within specific functional domains in normal and stroke-damaged cortex. This technique represents a facile approach for targeted delivery of viral vectors that should assist in the study of cell types and circuits in the cortex.
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