Cajal and Neural Circuits
By Javier De Felipe
A hypothesis on the organisation of the nervous system
In the times of Cajal, the prevalent hypothesis on the organisation of the nervous system was the reticular theory, which argued that the elements of the nervous system formed a web-like continuum by means of their propagations (dendrites and axons). This theory, later proven wrong, was conceived originally by Joseph von Gerlach (1820-1896). The success of this theory was due partly to the thought that if the nervous system was a continuous, uninterrupted web of propagations, it would be easy to explain how the flow of nervous information passed from one part of the brain to another. That is, the flow of information from one nervous cell to another could happen thanks to the continuity between their propagations. And then, in 1873, Golgi created the method of the reazione nera (black reaction.) For the first time, a histological preparation allowed the observation of all the parts of a nervous cell (the soma, dendrites and axon.) So it was observed that neurons have a very complex arborisation at the axons and dendrites, to the extent that if a region of the brain was chosen and every neuron in it, with its dendrites and axons, were to be stained, the result would be such an extraordinarily dense tangle of somata, axons and dendrites that it would be impossible to analyse it. Another advantage of the Golgi method is that several cells could be stained in a single preparation—albeit only a small number of them—so that individual nervous cells could be studied as well as the possible connections between them. Yet, despite the excellent results of the Golgi staining method, Golgi himself remained the most salient supporter of the reticular theory, proposing that dendrites had open ends but that axon collaterals anastomosized and formed an extensive network, thus suggesting that the nervous system consisted of a rete nervosa diffusa(diffuse nervous web), supporting in part the reticular theory of Gerlach. Golgi always held on to this conviction, which he defended even in the lecture he gave when he was awarded the Nobel Prize along with con Cajal.
In the first article he published after using the Golgi method, Cajal confirmed Golgi’s observation that dendrites had free ends, but also added another, crucial to the neuron doctrine, that this was also the case of axon collaterals, which would then form a “free” arborisation (without anastomosis.) He asserted that “each [nervous cell] is a fully autonomous physiological canton” (Cajal, 1888). Thus, from the beginning Cajal conceived of nervous cells as functional and anatomical units that communicated with each other by means of contact or contiguity, not by continuity. Cajal continued to furnish numerous observations that supported the neural doctrine in various parts of the nervous system in different animal species. Between 1888 and 1892 he published over 30 articles, which were summarised in his first review of the structure of the nervous system (Cajal, 1892), clearly formulating the neuron doctrine. The results of these early studies were so decisive that they constituted the core of the classical and influential literature review article in support of the neuron doctrine published by Wilhelm von Waldeyer-Hartz (1836-1921) in 1891. In it, this scientist used the term neuron to refer to the nervous cell (Waldeyer, 1891). Cajal summarised his own contributions to the neuron doctrine in several articles and books, particularly in the essay ¿Neuronismo o reticularismo? (Neuronism or reticularism? Cajal, 1933). Thanks to the introduction of the electronic microscope in the 1950s, along with the development of new methods to prepare nervous tissue for ultrastructural analysis, it was possible to examine the ultrastructure of the synapsis to confirm one of the main tenets of the neural doctrine: the presynaptic and postsynaptic elements are separated physically by a space about 10 to 20 nanometres wide, which is known as the synaptic cleft (see DeFelipe, 2007).
The law of dynamic polarisation
The neuron doctrine involved a radical shift in the conception of how information could flow within an “infinitely fragmented” brain, as opposed to a continuous neural reticulum. That is, it remained to be known how the nerve impulse travelled from one nerve cell to another across a physical gap. One of the significant offshoots of Cajal’s neuron doctrine was the theory of the law of dynamic polarization of nerve cells, which he proposed to explain the transit of nerve impulses through neural circuits. At the time it was believed that the function of dendrites was mainly one of nourishment, and that axons transmitted nerve impulses out of the cell (a generalisation based particularly in the logical conduction pattern shown by motor neurons from the spinal cord to skeletal muscles.) In 1889, Cajal proposed that at least in some cases dendrites functioned as current receptors (Cajal 1889), and two years later (Cajal 1891) he attempted to generalise this idea with the law of dynamic polarization, which was based on the direction followed by impulses in different regions of the nervous system where the anatomical path that had to be followed by nerve impulses was evident, such as the retina and the olfactory bulb (from the outer world to the inner world of the nervous system.) Thus, he proposed that neurons could be divided in three different functional regions: a receptor apparatus (consisting of the dendrites and the axon), an emitting apparatus (the axon), and a distribution apparatus (the axonal terminal arborisations.) Later on, Cajal realised that the soma does not always intervene directly in the conduction of the impulses, and that sometimes the nervous current goes directly from the dendrites to the axon (Cajal, 1897). Consequently, the law of dynamic polarisation gave way to the theory of axipetal polarisation. These studies had a great influence on the scientists of his age, and the observations and theories of Cajal were proven in their essence.
