Widespread Transduction of Mouse Neocortical Neurons by Subarachnoid Injection of AAV2

Recombinant adeno-associated viruses are a flexible and powerful tool for the delivery and expression of various genes of interest in many areas of experimental biology, particularly in neuroscience. The most popular method to drive the expression of a desired transgene in a particular brain area is to inject an AAV vector directly into the brain parenchyma. However, this method does not allow widespread neuronal transduction that is required for some in vivo experiments. In this article, we present a new technique for widespread gene expression in the mouse neocortex based on viral infusion into the subarachnoid space of the brain. This neuronal labeling method not only ensures widespread transduction of neurons in adult mouse superficial neocortical layers but also results in expression of the transgene in a large population of layer five pyramidal neurons with high specificity even when using a strong non-selective promoter such as CAG. Moreover, because cell transduction takes place at a significant distance from the injection site, this method can help preserve brain tissue for subsequent optical or electrophysiological recordings of neuronal activity.