Cajal's vision of a neuronal cytoskeleton
One hundred years ago, Santiago Ramón y Cajal was obliged to open a new front in his battle to prove that the nervous system is constituted of discrete units. Just as the neuron doctrine was beginning to gain momentum among neurologists, it was threatened once again by a recently reinvigorated theory claiming that nerve impulses might after all be conducted over an uninterrupted network. According to this view, the actual conductors were not the anastomosed nerve fibers and cells per se, as was postulated by the original reticulum model, but so-called "neurofibrils" threaded through the fibers and cells as a continuous cable-like system which ran across long distances in the animal body. Stephan von Apáthy and Albrecht Bethe, in particular, had succeeded in showing crisply stained neurofibrils within, and apparently passing between, series of nervous elements in various invertebrates and vertebrates.
The new theory admitted the numerous evidences indicating that nerve cells and their processes are immediately contiguous though not continuous with each other, and in fact required this condition in order to guarantee an adequate electrical insulation for the neurofibrils presumably conducting impulses within. Yet it also agreed with the widely accepted concept of a functionally continuous nervous system. Therefore, this was a reasonable and experimentally supported compromise between the positions held by the defenders of the reticulum model and the proponents of the neuron doctrine. However, none of all this pleased Cajal, who at once arose to save the neurons from being regarded as mere protective envelopes for the allegedly conducting neurofibrils. Thus, the Spanish histologist became one of the forerunners in the investigation of the neuronal cytoskeleton.
This relatively little known aspect of the history of the neuron doctrine is examined on the basis of Cajal's representative writings on the matter. He started by mastering the staining methods used by Apáthy and Bethe to reveal neurofibrils, and then applied a novel and still better procedure developed by his friend Luis Simarro. The initial public response, presented at the XIX International Congress of Medicine (1903), was vehemently critical of the continuous conductor line interpretation, insisting that neurofibrils are strictly intracellular and that they in no case extend out of a given cell. The following year, in a more relaxed mood, he patiently reported in a series of papers his own keen observations of neurofibrillar arrangements within nerve cells in a variety of specimens, from earthworms up to the vertebrate retina. Finally, his mature conclusions on this topic, which could not be included in the original version of the monumental treatise on the texture of the vertebrate nervous system (1899-1905), found their way a few years later into the French translation revised and updated by the author. Here Cajal distinguished two classes of fibrils forming the intracellular network: "a) thick spans or primary filaments [...] which run in the same direction as the [cell] processes, [and] become strongly colored by the reactants; b) fine or secondary spans, paler and more weakly colorable, [which] have varying orientations and join the primary filaments with each other in such a way as to make of the protoplasmic skeleton a unitary whole." (Ramón y Cajal, 1909, p. 179). The last five words suggest a visionary notion that hardly anyone else had at the time.
Session VI -- Anatomical and Physiological Models and Techniques
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