An AAV capsid proposed as microglia-targeting directs genetic expression in forebrain excitatory neurons.

A newly developed capsid AAV-MG1.2 was reported to mediate specific microglial transduction. However, we find that AAV-MG1.2 actually enables specific genetic access to excitatory neurons in forebrain regions including hippocampal formation and visual cortex but does not confer expression in microglia or astrocytes in vivo. Furthermore, we find that AAV-MG1.2 specifically labels the deep layer of the CA1 pyramidal layer in a titer-dependent manner. We show that AAV-MG1.2-Cre can be used to genetically target excitatory neurons for cell-type-specific neural circuit mapping studies. We also find that AAV-MG1.2 conserves specificity for excitatory neurons in rat hippocampus. Thus, the AAV-MG1.2 presents a useful viral-genetic tool for targeting excitatory neurons in the forebrain across different species.