Ramón y Cajal's early work was accomplished at the Universities of Zaragoza and Valencia, where he focused on the pathology of inflammation, the microbiology of cholera, and the structure of Epithelial cells and tissues. It was not until he moved to the University of Barcelona in 1887 that he learned Golgi's silver nitrate preparation and turned his attention to the central nervous system. During this period he made extensive studies of neural material covering many species and most major regions of the brain.
Ramón y Cajal made several major contributions to neuroanatomy. He discovered the axonal growth cone, and provided the definitive evidence for what would later be known as "neuron doctrine", experimentally demonstrating that the relationship between nerve cells was not one of continuity, but rather of contiguity. "Neuron doctrine" stands as the foundation of modern neuroscience. In the debate of the neural network theories (neuron theory, reticular theory) Ramón y Cajal was a fierce defender of the neuron theory.
He provided detailed descriptions of cell types associated with neural structures, and produced excellent depictions of structures and their connectivity.
He was an advocate of the existence of dendritic spines, although he did not recognize them as the site of contact from presynaptic cells. He was a proponent of polarization of nerve cell function and his student Rafael Lorente de Nó would continue this study of input/output systems into cable theory and some of the earliest circuit analysis of neural structures.
He discovered a new type of cell, to be named after him: the interstitial cell of Cajal (ICC).[7] This cell is found interleaved among neurons embedded within the smooth muscles lining the gut, serving as the generator and pacemaker of the slow waves of contraction that move material along the gastrointestine, vitally mediating neurotransmission from motor nerves to smooth muscle cells.
In his 1894 Croonian Lecture, he suggested in an extended metaphor that cortical pyramidal cells may become more elaborate with time, as a tree grows and extends its branches. He also devoted a considerable amount of his time to studying hypnosis (which he used to help his wife with birth labor) and parapsychological phenomena, but a book he had written on these areas got lost during the Spanish Civil War