Ventral skull based approach to whole-brain extraction in mice.

Head fixation combined with cranial window, GRIN lens, or prism implantation are common techniques in systems neuroscience for real-time imaging of neural activity. A critical step in these experiments is the removal of these implants and subsequent histological processing to assess tissue integrity and verify opsin expression. However, removing implants from the dorsal surface of the skull often causes traumatic damage to the underlying cortex. This study introduces a novel technique for intact brain excision that removes dorsal implants while preserving cortical integrity. Instead of the conventional dorsal approach, which often risks cortical damage, the skull is resected from the ventral side, allowing the implant to remain in place for post-mortem analysis. This approach:•Enables dorsal implants to remain embedded in the brain during fixation.•Improves reproducibility by standardizing the extraction method, reducing variability introduced by traditional dorsal implant removal.•Preserves tissue integrity that would otherwise be compromised by removing the implant from fresh brain tissue.