Abstract
This article gathers together different opinions on the current status and future directions of the study of the brain, taking as a working document the article “The anatomical problem posed by brain complexity and size: a potential solution” http://journal.frontiersin.org/article/10.3389/fnana.2015.00104/full. These commentaries are followed by a section dedicated to a general discussion of the issues raised, in which all contributors participate. The authors who have contributed to this article are listed in alphabetical order. As the reader will see, there are different points of view and of course there are many other aspects that would need further discussion that have been raised by other scientists who did not participate directly. For example, Peter Somogyi made the following comment (personal communication): [“Anatomy” is a discipline and not a biological entity that exists in nature. Hence the brain or its cells do not have anatomy; we study them with anatomical methods (usually using microscopes) while we carry out “anatomical analysis.” The brain, its nuclei, cells, and their parts are the biological entities which several disciplines study, preferably together, providing a unified description and explanation of them. We must be clear about this, and avoid terms like “anatomical properties,” “physiological properties,” or “biochemical properties” as if these somehow existed in isolation. The separate disciplines, which developed historically due to the limitation of individual human brain capacity and short life span leading to methodological and conceptual specialization, are based on sets of methods, but study the same indivisible biological entity. E.g., the synaptic current recorded by electrophysiological methods flows through the membrane that we see in the electron microscope or with the help of antibodies to synaptic ion channels in the light microscope. Accordingly, the “anatomical problem” exists because of inadequate scientific rigor in addition to methodological limitations that are often not understood, not because of “brain complexity”.] This is just an example of the many possible different points of view when dealing with the subject of the anatomy of the brain. Thus, this article is not intended to be comprehensive, and the unavoidable limitations in the selection of comments, data, and their interpretation reflect, in many cases, the personal views and interests of the authors.
Highlights
This quest for detailed structure flies under the flag of “Connectomics,” but in practice the “Connectome” is a grab-all that describes any kind of map of structural and functional connectivity at various scales: So the human connectome is mentioned in the same breath as the 302 neurons of the C elegans connectome
The rise of model organisms for studying brain architecture, in particular the mouse with its range of options for genetic targeting and manipulation, has dramatically accelerated the study of conserved features of mammalian brain organization but leaves largely unaddressed a fundamental problem: how similar is the rodent brain, or for that matter the non-human primate brain, to the human brain and how far can we push these models as proxies for studying the human brain itself? The generally dismal experience of the pharmaceutical industry in the use of the mouse as a preclinical model provides a sobering backdrop for the premise of species conservation, and we find ourselves with a dual problem
A good example of this predictive approach would be the observation by Tyler et al (2015) that layer II and III pyramidal neurons show different electrophysiological and structural properties depending on their precursor cell type of origin
Summary
A variety of “highthroughput” methods offer to refine our understanding of the detailed neuronal circuitry -and thereby their signaling (on the basis of Francis Crick’s dictum that knowledge of function follows automatically from a detailed knowledge of the structure) This quest for detailed structure flies under the flag of “Connectomics,” but in practice the “Connectome” is a grab-all that describes any kind of map of structural and functional connectivity at various scales: So the human connectome is mentioned in the same breath as the 302 neurons of the C elegans connectome. Determining where such regularities exist, and describing their forms and frequencies, should be the first strategic action of any largescale neuroanatomical research program It is astonishing (to us) that there are few qualitative descriptions of cortical circuits (albeit even Ramón y Cajal was challenged to do this) and vanishingly few quantitative data describing cortical networks in different species and areas. Because the cortex is critically involved in intelligent behavior, an understanding of its self-construction is expected to yield insights into the principles of processing in those circuits useful both for neuroscience, and for developing neurally based computational technologies
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