Modified Golgi-Cox method for micrometer scale sectioning of the whole mouse brain

Abstract

One of the major challenges of connectomics is obtaining a physical map of the neurons that comprise a circuit and the sites within the whole mouse brain. However, there is no report that addresses the preparation of whole mouse brain tissue for microsectioning. In this paper, such tissue is prepared by a modified Golgi-Cox method in which the staining time is prolonged to half a year, the darkening solution is changed to 1% LiOH, and the brain is embedded in resin. Projections of several coronal sections are reconstructed by serial 1-μm sectioning and simultaneous imaging of the specimen. This approach ensures that the stained neurons are present throughout the whole mouse brain from superficial to deep layers and that the neuronal soma and traces of the processes can be distinguished in local magnification.