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Javier de Felipe

Journey to the interior of the brain through Cajal URL: http://www.march.es/conferencias/anteriores/voz.aspx?p1=21583&l=2

One of the main goals of neuroscience is understanding the biological mechanisms responsible of the activity in the human mind. Without doubt, the brain is the most interesting and enigmatic organ of the human body, not only because it governs our organism, but also because it controls our behaviour and allows us to communicate with other living beings. Particularly, the study of the cerebral cortex is the largest challenge of the coming centuries, as it represents the fundaments of our humanity; this is, the activity of the cerebral cortex is related with the capacities that differ humans from the rest of mammals. Thanks to the notable development and evolution of the brain, we are capable of doing extraordinary and extremely complex tasks such as writing a book, composing a symphony or inventing a computer. Without doubt, science has advanced dramatically in the last decades allowing us to study the human brain from all kind of angles -molecular, morphology, physiology and genetic-, although we have only come to scratch the surface of mysteries it holds. Even if it may sound surprising, we still lack answers to many of the basic questions in neuroscience, such as: What is the neuronal substrate that makes us humans? How is the brain altered, and how diseases like schizophrenia, Alzheimer, or depression are produced? How does the brain integrate simultaneously the information that is processed in the different cortical areas in order to provide us with a unified, continuos and coherent perception? All these fundamental questions, and many others, still lack answer even though we are witnessing many scientific advances in the present.

Among the favorite topics of Cajal was the study of the human neocortex and the butterflies of the soul, as he beautifully described in a metaphoric sense the pyramidal cells. Currently, we are aware that pyramidal cells are the main source of cortical exciting synapses and virtually the only projecting cell of the cerebral cortex. Thus, the information processed in a certain region of the cortex is transported from there through the axons of the pyramidal cells in order to reach other regions of the cortex or subcortical centres. On top of that, they are also the key elements for the columnar organization of the cerebral cortex, and of the linkage mechanisms in the global process of sensory perception. These are some of the reasons why the study of pyramidal cells is of maximum interest. Furthermore, the dendritic spines of the pyramidal cells are a crucial component for the structure and roles of these cells, which explains why this is one of the main lines of research in the present.

Comparative studies between the different cortical regions and between species, mainly between humans and non-human primates,  have been done by applying sophisticated methodologies to analyze pyramidal cells. For example, it has been observed that the pyramidal cells from from the human temporal cortex have approximately twice the dendritic spines of a macaque or a titi monkey, and around 5 times more than the somatosensory cortex of a mouse. Similarly, the pyramidal cells of the human prefrontal cortex show around 72% more dendritic spines than the cells of the macaque prefrontal cortex, and approximately 5 times more than titi monkey prefrontal cortex or the mouse motor cortex. These data indicate that the pyramidal cells of the human cerebral cortex can integrate many more afferences than those from any other species studied, and that there are significant differences between the cortical areas, and between species.

In addition, the number of symmetric (inhibiting) and asymmetric (exciting) synapses per neuron have been observed using electronic microscopy, and this number in humans is much higher than in mice and rats, which means a much higher complexity in the exciting and inhibiting circuits. Also, significant differences between species have been noted when it comes to proportion and types of GABAergic interneurons (inhibiting). One of the most important examples is the existence of a special type of GABAergic interneuron named double bouquet cells. These cells were discovered by Cajal in the human cerebral cortex, and are characterized by long axon collaterals - which produce vertical beams densely grouped (like a horse tail)- and due to being very numerous and producing a microcolumnar structure with a very regular distribution. Considering that each horse tail establishes hundreds of inhibiting synapses with dendritic spines and arbors within the narrow field of vertical distribution of the axonal branches, it is believed that double bouquet cells represent a key element for the microcolumnar organization of the neocortex. Nevertheless, this microcolumnar organization has only been observed in man and other primates, but never in rodents (rats and mice), lagomorphs (rabbits), artiodactyles (goats) and carnivores (cat, lion, dog), which suggests there are fundamental differences in the organization of the cerebral cortex between species.

To conclude, it is probable that as new, detailed human cortex microanatomical studies are published, further differences between humans and other species will be discovered. Of course, we do not know what is the exact meaning of these structural variations when it comes to correlating them with human and other animal species characters, but we believe that these observations take us one step further into tackling the passionate topic of studying the neural substrate that makes us humans.  

 

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