Symposium: ‘A celebration of neuroanatomy in the centennial of Cajal's Nobel Prize’

By 1889, at the age of 37 years, Cajal had published two papers on neuroanatomy in the Revista trimestral de Histología normal y patológica, which he had founded (and subsidised) the previous year. However, his ideas received hardly any attention from his colleagues and he became a ‘little alarmed by their silence’ (Ramón y Cajal, 1981). He admitted that most histologists had not read his papers since ‘it is true that Spanish is an unknown language to the educated’ and he thought that the ‘direct objective demonstration’ of facts would be more convincing. Therefore, he first translated his principal papers into French and then decided to show his histological preparations to scientific colleagues, in order to demonstrate his findings and ideas. To this end, Cajal applied for membership of the Anatomische Gesellschaft, asked his Rector for permission to travel, collected all of his savings and set out for Berlin, where the Anatomische Gesellschaft met in October 1889.

Cajal travelled to Berlin carrying, ‘as a precaution’, his own ‘excellent Zeiss microscope’ and a collection of his best slides. He paid hardly any attention to the oral presentations at the meeting, due to his ‘impatience’ and ‘lack of attention’. Instead, he set up his microscope very early in the demonstration room, unpacked his slides, set up the most informative sections and started to explain ‘in bad French’ the content of his preparations. Few specialists paid attention to him because ‘each attends his own interests; after all it is natural to prefer to show one's own work than to examine others’ work’. However, some important scientists, notably His, Schwalbe, Retzius, Waldeyer, and particularly Kölliker, showed an interest. At the end of the session, Kölliker, the ‘venerable patriarch of German Histology’, took him ‘by carriage’ to the luxurious hotel where he was staying, invited him to lunch and introduced him to other important German histologists and embryologists. Kölliker even learnt Spanish in order to read Cajal's early papers and translated some of them into German, to be published in his Zeitschrift für wissenschaftliche Zoologie. Cajal was ‘vividly grateful’ to Kölliker for his important role in getting Cajal's work accepted and described him as endowed with ‘great observational talent’, ‘unfailing laboriousness’, ‘charming modesty and exceptional rightness and judgement serenity’.

In September 2006, one hundred years after the Nobel Prize in Medicine was awarded jointly to Santiago Ramón y Cajal and Camilo Golgi, the Anatomical Society of Great Britain and Ireland and the Sociedad Anatómica Española held their first joint meeting at the Faculty of Medicine, Universidad Complutense de Madrid. A major event within this meeting was the symposium entitled A Celebration of Neuroanatomy in the Centennial of Cajal's Nobel Prize. The symposium presented an occasion to gather together an outstanding group of neuroanatomists who have contributed a selected group of papers that make up this special issue of Journal of Anatomy. This volume incorporates manuscripts arising from the symposium. The first two papers deal with aspects of the evolution of the brain. Moreno and González review the literature indicating that the amygdaloid complex of amniotes shares basic developmental, hodological and neurochemical features, with derivatives from the lateral, ventral and subpallium contributing to its formation. They then present evidence to demonstrate that most of the amygdaloid structures present in amniotes are recognizable in anamniote anuran amphibians. This evidence strongly suggests that basic amygdaloid structures were present at least in the brains of ancestral tetrapods and that the amygdaloid complex of all tetrapods follows the same basic plan. Cheung et al. investigated the sites of cell proliferation in the embryonic reptile and bird brain, in order to shed light on the evolution of the mammalian cortex. They show that in the turtle embryo, cell proliferation largely occurs in the ventricular zone throughout the brain. However, in the chick embryo, a subventricular proliferative zone is present in both pallial and subpallial regions of the ventral telencephalon. Therefore, the authors have provided new evidence to support the suggestion that the elaboration of the subventricular zone, as revealed in the embryonic chick brain, was the major driving force behind the evolution of the six-layered neocortex in mammals.

Ahsan et al. review current evidence suggesting that the early axon scaffold established in the embryo provides the basic structure for the later, more complex axonal pathways in the brain. They describe how the ventral longitudinal tract is pioneered by neurons located at the ventral midbrain-forebrain boundary, which form the medial longitudinal fascicle. They go on to demonstrate how patterning molecules, notably Shh, are involved in the formation of medial longitudinal fascicle neurons and in the guidance of their axons. They then describe the expression of several homeobox genes (that are expressed downstream of Shh) in the tegmentum and review the evidence of their molecular interactions and involvement in neuronal fate specification. Continuing in a developmental vein, Andrews et al. review the literature demonstrating that mammalian cortical interneurons are generated in the ganglionic eminences in the subpallium and are guided along tangential migratory paths to reach the cortex, by intrinsic and extrinsic cues. Recent evidence suggests that the family of Slit proteins, acting through Robo receptors, play a role in guiding the migration of cortical interneurons, as well as their role in axon guidance in the developing forebrain. The authors provide new information about the patterns of expression of Slit and Robo during forebrain development and review the evidence supporting their role in cortical interneuron migration.

The largest part of this volume deals with aspects of mammalian cortical architecture, cytology and connectivity. In their review, Belmalih et al. describe the development of cortical architectonics as a branch of neuroanatomy and examine its validity for accurately defining functionally different cortical fields. They go on to demonstrate, using the macaque agranular frontal cortex as a model, that by combining cyto-, myelo- and immuno-architectonic approaches, architectonic borders can be reliably and consistently defined across individuals. Furthermore they demonstrate that this approach can be used to precisely define functionally distinct areas of cortex and to predict the existence of new functional areas.

In their review, Benavides-Piccione and DeFelipe describe the distribution of tyrosine hydroxylase immunoreactive interneurons in the mammalian cortex, particularly in humans in which they are notably abundant. The authors argue that tyrosine hydroxylase immunoreactive neurons are involved in a larger variety of cortical circuits in man than in other species and that the marked regional variation in the distribution of these interneurons suggests a variability in the organisation of cortical microcircuits that probably reflects an evolutionary adaptation to a particular function. Mendizabal-Zubiaga et al. review previous and present new work on spiny inverted neurons (inverted pyramidal neurons) that are most commonly located in layers V–VI of mammalian neocortex. These neurons project to other regions of the cortex, the claustrum and striatum, but do not appear to project outside of the telencephalon. They give rise to the majority of cortical input to the primary visual cortex and from the primary visual cortex to the striatum. The authors provide an insight into how the morphology of these neurons underlies their function. Developing the theme of cortical circuitry, Barbas describes the sequential and collaborative interactions of the anterior temporal sensory association areas, posterior orbitofrontal cortex and the amygdala in evaluating the sensory and emotional aspects of the environment for decision making and action, in complex behaviour. In view of the fact that the hippocampal formation plays an important role in episodic memory formation and consolidation and these memories are constructed from cortical information that is channelled through the entorhinal cortex to the hippocampus, Mohedano-Moriano et al. investigated the nature and distribution of cortical inputs to the entorhinal cortex. The authors describe the heterogeneous topographical distribution of these inputs and discuss them in relation to the established neuroanatomy of the entorhinal cortex. Finally, Tavares and Lima describe the role of the dorsal reticular nucleus and caudal ventrolateral medulla systems in controlling nociceptive transmission in the spinal cord. In particular, the way in which the ascending branch of the spino-dorsal reticular nucleus loop is inhibited by spinal GABAergic neurons, which probably buffer the amplifying effect of the dorsal reticular nucleus and how the caudal ventrolateral medulla triggers intense descending inhibition in acute pain, but promotes nociceptive transmission in chronic pain. The authors conclude with the suggestion that this modulatory shift is related to decreased expression of µ-opioid, δ-opioid and GABA_B receptors in the caudal ventrolateral medulla and that this may provide a possible therapeutic approach to relieve chronic pain by controlling neurotransmitter release using gene therapy.

The papers arising from the symposium are a fitting tribute to Cajal's legacy. Athough we no longer fund private journals or travel by carriage, Cajal's experiences, thoughts and concerns appear remarkably contemporary. We continue to attend scientific meetings, contact colleagues, try to persuade them of the value of our work and enjoy genuine personal and scientific friendship. We hope that many such friendships were forged at the symposium in Madrid.