Viral Vector Eluting Lenses for Single‐Step Targeted Expression of Genetically‐Encoded Activity Sensors for in Vivo Microendoscopic Calcium Imaging

Abstract Optical methods for studying the brain offer powerful approaches for understanding how neural activity underlies complex behavior. These methods typically rely on genetically encoded sensors and actuators to monitor and control neural activity. For microendoscopic calcium imaging, injection of a virus followed by implantation of a lens probe is required to express a calcium sensor and enable optical access to the target brain region. This two‐step process poses several challenges, chief among them being the risks associated with mistargeting and/or misalignment between virus expression zone, lens probe and target brain region. Here, an adeno‐associated virus (AAV)‐eluting polymer coating is engineered for gradient refractive index (GRIN) lenses enabling the expression of a genetically encoded calcium indicator (GCaMP) directly within the brain region of interest upon implantation of the lens. This approach requires only one surgical step and guarantees alignment between GCaMP expression and lens in the brain. Additionally, the slow virus release from these coatings increases the working time for surgical implantation, expanding the brain regions and species amenable to this approach. These enhanced capabilities should accelerate neuroscience research utilizing optical methods and advance the understanding of the neural circuit mechanisms underlying brain function and behavior in health and disease.