Removable cranial window for sustained wide-field optical imaging in mouse neocortex

Attempts to image neocortical regions on the surface of mouse brain typically use a small glass disc attached to the cranial surface. This approach, however, is often challenged by progressive deterioration in optical quality and permits limited tissue access after its initial implantation. Here we describe a design and demonstrate a two-stage cranial implant device developed with a remarkably versatile material, polydimethylsiloxane, which facilitates longitudinal imaging experiments in mouse cortex. The system was designed considering biocompatibility and optical performance. This enabled us to achieve sustained periods of optical quality, extending beyond a year in some mice, and allows imaging at high spatio-temporal resolution using wide-field microscopy. Additionally, the two-part system, consisting of a fixed headplate with integrated neural access chamber and optical insert, allowed flexible access to the underlying tissue offering an expansive toolbox of neuromanipulation possibilities. Finally, we demonstrate the technical feasibility of rapid adaptation of the system to accommodate varying applications requiring long-term ability to visualize and access neural tissue. This capability will drastically reduce wasted time and resources for experiments of any duration, and will facilitate previously infeasible studies requiring long-term observation such as for research in aging or the progression chronic neurological disorders.