Screening AAV delivery routes, capsids, and promoters for cortex-wide functional and long-term stable access to brain function in large-brain species

How signals relevant to behavior and cognition are processed within neural circuits, engaging thousands of neurons across multiple brain regions remains a central question. After decades of research, our current understanding of brain-wide neural circuits enabling various brain functions in non-rodent species (e.g., cats and primates) remains limited. In stark contrast, significant progress has been made in dissecting mouse brain function, enabled by the availability of transgenic driver and reporter lines.We set out to emulate the quality and reproducibility of transgenic mouse reporter lines in non-rodent models by establishing a long-term stable gene delivery method that achieves functional protein levels across the brain. We quantified transduction efficiency upon screening a set of constructs in the cat brain. We identified one construct that yields brain-wide labeling upon a single injection. Our result provides a precise, highly reproducible brain-wide transduction method, potentially approximating the qualities attributed to transgenic reporter mouse lines. Using this method, genetically-targeted dissection of both local and brain-wide functional circuits may gain broader application in non-rodent models.