The Cajal School in the Peripheral Nervous System: The Transcendent Contributions of Fernando de Castro on the Microscopic Structure of Sensory and Autonomic Motor Ganglia

Abstract

The fine structure of the autonomic nervous system was largely unknown at the beginning of the second decade of the 20th century. Although relatively anatomists and histologists had studied the subject, even the assays by the great Russian histologist Alexander Dogiel and the Spanish Nobel Prize laureate, Santiago Ramón y Cajal, were incomplete. In a time which witnessed fundamental discoveries by Langley, Loewi and Dale on the physiology of the autonomic nervous system, both reputed researchers entrusted one of their outstanding disciples to the challenge to further investigate autonomic structures: the Russian B.I. Lawrentjew and the Spanish Fernando de Castro developed new technical approaches with spectacular results. In the mid of the 1920's, both young neuroscientists were worldwide recognized as the top experts in the field. In the present work we describe the main discoveries by Fernando de Castro in those years regarding the structure of sympathetic and sensory ganglia, the organization of the synaptic contacts in these ganglia, and the nature of their innervation, later materialized in their respective chapters, personally invited by the editor, in Wilder Penfield's famous textbook on Neurology and the Nervous System. Most of these discoveries remain fully alive today.

Keywords: Nobel Prize; Santiago Ramón y Cajal; chemoreceptors; development; history of neuroscience; spanish neurohistological school; superior cervical ganglion; synapse.

Figure 1

A tribute to some pioneers of the study of the autonomic nervous system. (A) Photographic self-portrait of Santiago Ramón y Cajal; his profile is outlined by a chalk sketch of a human brain. (B) Portrait of the recognized Russian histologist Alexander Dogiel. (C) The Russian neuroscientist Lawrentjew looking at the microscope. (D) A detailed drawing from a sympathetic neuron by Santiago Ramón y Cajal, as a good example of the neuronist interpretation of the fine structure of the nervous system. (E) Dogiel’s interpretation of neurons from the Auerbach plexus (published in: Dogiel, 1899), a good example of reticularist vision of the organization nervous system (A–D) are part of Archive Fernando de Castro.

Figure 2

First works of Fernando de Castro in the structure of the peripheral nervous system. (A) Image from the original PhD thesis of Fernando de Castro, with his hand-drawn illustrating some pathological forms of neurons from the Gasser’s ganglion from a patient of osteomalacia. The typewritten figure legend (in Spanish) for the defense of the thesis is conserved for the reader, as well as the signature from de Castro at that time. This figure was published in de Castro (1922). (B) de Castro’s original hand-sketch of a portion of a sympathetic lumbar ganglion in normal condition (human, 38-year old) originally stained with the Cajal’s method, and illustrating preganglionic (a) and intraganglionnic endings (d) over dendritic bushes, accesory dendrites forming bushes (b,g), a protoplasmic process forming collaterals (c) and a pericellular dendritic nest (f). This schema was published in de Castro (1923c, 1933). (C) Image of a young Fernando de Castro (1922) at his family house in Cercedilla, in the mountains close to Madrid (A–C) are part of Archive Fernando de Castro.

Figure 3

Sympathetic neurons by Fernando de Castro. (A) de Castro’s hand-made schematic illustration of sympathetic neurons stained with the Cajal’s method, showing short long (a –the axón arises from this dendrite at a distance from the soma, c), short dendrites (b). This image was published in de Castro (1933). (B) Partial view of a sympathetic ganglion (normal condition) of an adult cow (de Castro, 1937). (C) Portion of a sympathetic ganglion with regenerated preganglionic fibers (a) after a vagus-sympathetic crossed anastomosis (de Castro, ; A) is part of Archive Fernando de Castro.

Figure 4

Some proofs of the long-term friendship developed by Fernando de Castro with other disciples and visitors of the laboratory of Santiago Ramón y Cajal. (A) Manuscript letter from Rafael Lorente de Nó to Fernando de Castro describing the excellent formation and situation of de Castro in the neuroscientific panorama of the mid 1920’s. (B) Original charcoal portrait of Fernando de Castro by Ferenc Miskolzy (made in 1926, in Madrid), Hungarian painter and brother of the founder of modern Hungarian Neurology, Deszo Miskolzy, disciple and translator of Cajal’s books and close friend of de Castro for years. The painter came to Spain because he wanted to visit exiled last Austro-Hungarian empress, Zita, exiled in Spain. Following recommendations of his brother Deszo, he visited Fernando de Castro at Madrid, who showed him his scientific drawings and his deep interest and knowledge in Art. The painter gifted this charbon portrait to the Spanish neuroscientist as a proof of the close frienship of both Miskolzy brothers and Fernando de Castro. (C) Madrid (Spain), December 1958, from the left to the right, Florencio Bustinza (1902–1982; born at Liverpool, pharmacologist and profesor of Biology at Madrid), Sir Howard Florey (Nobel Prize in Physiology or Medicine 1945) and Fernando de Castro. Bustinza was personal friend of Sir Alexander Fleming and Sir Howard Florey since 1948, and Fernando de Castro kept frienship with the latter since his time at Cajal’s laboratory to learn histological technique during the mid 1920s, (A–C) are part of Archive Fernando de Castro.

Figure 5

Post-war de Castro on the autonomic nervous system and their synaptic structure. (A) Electromiographic recordings of the nictitant membrane of the adult cat where the sympathetic superior cervical ganglion has been innervated by rami from the VI-c and VII-c nerves (de Castro and Herreros, 1945). This 10 s-recording shows that the intensity of the contraction correlates with the frequency of the tetanic stimulation. (B) Schematic representation of the preganglionic convergence of fibers (a, b, c) onto ganglionic cell types (A, B, C). The thickness of the fibers is representative of their thickness in vivo. In this it is assumed that ganglion cells can trigger when activated by two boutons simultaneously, or in the slow fibers (c) when a sinchronic impulse via a-b facilitates it (de Castro and Herreros, 1945). (C) Original letter from Rafael Lorente de Nó to Fernando de Castro (dated at the Rockefeller Institute, New York on January 30th, 1947): “Dear Fernando, Wait at the shipboat till the arrival of Valdecasas or Gallego. Gallego will come with you to New York and will bring you to your accomodation, that is worthy and economic. Hugs, Rafael” (translated by the autor of this work from Spanish). (D) Antonio Gallego (1915–1992) and Fernando de Castro on board of the Motomar steamship, in their way back to from New York to Spain (1947) after their respective first scientific experience at the USA. (E) Fernando de Castro (at the microscope), invited speaker to expose the cytoarchitecture of the autonomic nervous system. Became one of the main characters in the final offical defeat of reticularists at the 34 Tagung Deutschen Gesselchaft fü Pathologie (Wiesbaden, Germany; 1950). His friend, the German histologist established in Chile, Emil Herzog (on foot, with glasses, just behind Fernando de Castro) acts as de Castro’s master of ceremony at that time, (A–E) are part of Archive Fernando de Castro.