The unending fascination with the Golgi method

Abstract Introduction In the second half of the 19th century, Camillo Golgi provided a breakthrough staining technique for visualising whole neurons, which are seen as black bodies due to intracellular staining with microcrystalline silver chromate. The high contrast, selective staining properties enabled identification of complete neuronal morphology. This staining technique, termed the Golgi method, was later improved by Ramón y Cajal and popularised through his tireless experiments. Morphological analysis, using the Golgi method, led to the discovery of neuronal microstructures such as dendritic spines and growth cones and helped give rise to the ‘neuron doctrine’. Many post-mortem human brains as well as brains of experimental animals have since been stained using this method. In combination with other morphological techniques (e.g. electron microscopy and immunohistochemistry), the Golgi method has allowed us to glean more information regarding the neuronal networks present in various brain regions. However, the Golgi method is a difficult first choice for morphological analysis since it is capricious, complicated and time-consuming and has poor reproducibility. Recent increases in the number of in vivo animal experiments and of post-mortem brains collected following neurological disorders heighten the need for the Golgi method to be viewed as a crucial morphological tool for assessing abnormalities in single neurons, as well as in neuronal networks. Fortunately, over 100 years of neuroanatomical diligence has seen significant contributions to overcoming the shortfalls of this method. The advent of modified Golgi methods with potential use as routine techniques, together with the development of the kit-based Golgi–Cox method, has made the Golgi method more accessible to neuroanatomists. This review surveys the technical fundamentals, history and evolution of Golgi methods and intends to spark an interest in the Golgi method within every neuroscientist, novice and old pro alike and to allow them to appreciate this useful technique. Conclusion Many neuroanatomists, including us, feel a strong attraction to the Golgi method as a powerful morphological tool. Our researchers have identified unwanted issues of the various Golgi methods and then have been working to remedy these problems. We encourage the reader to adopt staining using the Golgi method as its utility continues to evolve.