A polymeric, PDMS-based large-scale skull replacement suitable for optical and mechanical access for long-term neuronal imaging, electrophysiology, and optogenetics

Many techniques to record and manipulate neuronal activity across large portions of the vertebrate brain, such as widefield and two-photon calcium imaging, electrophysiology, and optogenetics, are now available. However, few effective approaches enable both optical and mechanical access to the brain. In this work, we offer an in-depth guide for synthesizing, implanting, and using polydimethylsiloxane (PDMS) windows as skull replacements for chronic optical neuronal imaging. Furthermore, we provide instructions to perform viral injections and multi-site silicon probe implantation.