UC San Diego

During adult neurogenesis, newborn neurons are selectively produced throughout adulthood in the hippocampus, a brain structure heavily involved in the processes of learning and memory formation. During hippocampal adult neurogenesis, intermediate neural progenitor cells (NPCs) in the dentate gyrus (DG) produce immature adult-born dentate granule cells (abDGCs), which integrate into existing neural circuits and contribute to pattern separation and pattern completion. To visualize the activity of newborn and developmentally-derived DGCs in-vivo, genetically encoded calcium indicators (GECIs) can be transfected into neuronal genomes with the use of viral vectors such as recombinant adeno-associated virus (rAAV). Although rAAV has become widely used as a viral vector due to its low pathogenicity and low immunogenicity, its effect on cells located in the hippocampus was previously unknown. Our experiments reveal that exposure of the DG to rAAV in experimentally significant doses leads to the death of intermediate NPCs and abDGCs in adult mice. This study demonstrates that the rAAV- induced ablation of adult hippocampal neurogenesis is dose-dependent, cell-specific, and time-sensitive.