Enhancers hit their targets

Genetic tools for accessing neuron subtypes have enabled countless discoveries about circuit structure and function. Compared to the highly specific tools available for nematodes and fruit flies, the mammalian toolkit lacks both precision and systematic coverage. In a new paper published in Cell, a team of researchers at the Allen Institute and partner institutions unveil an unprecedented suite of targeting tools for mammalian cortical circuits. Leveraging single-cell transcriptomic and epigenomic data, this team generated and screened over a thousand enhancer AAVs targeted to precise cell-type subclasses identified in recent cortical taxonomies. To maximize potential use across species, the authors selected enhancer sequences that are conserved across mouse and human genomes. They demonstrated improved specificity over prior methods in targeting an interneuron subclass that is critical for sleep, as well as novel access to numerous other subclasses. A group of papers co-published with this study demonstrate the utility of these tools for neural circuit research and report toolkits for targeting striatal and spinal cord populations. As these tools are publicly available, they provide a powerful new set of precision approaches for mammalian circuit dissection and control.

Original reference: Cell https://doi.org/10.1016/j.cell.2025.05.002 (2025)