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The anatomical problem posed by brain complexity and size: a potential solution.

DeFelipe J - Front Neuroanat (2015)

Bottom Line: Over the years the field of neuroanatomy has evolved considerably but unraveling the extraordinary structural and functional complexity of the brain seems to be an unattainable goal, partly due to the fact that it is only possible to obtain an imprecise connection matrix of the brain.The reasons why reaching such a goal appears almost impossible to date is discussed here, together with suggestions of how we could overcome this anatomical problem by establishing new methodologies to study the brain and by promoting interdisciplinary collaboration.Generating a realistic computational model seems to be the solution rather than attempting to fully reconstruct the whole brain or a particular brain region.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio Cajal de Circuitos Corticales (Centro de Tecnología Biomédica: UPM), Instituto Cajal (CSIC) and CIBERNED Madrid, Spain.

ABSTRACT
Over the years the field of neuroanatomy has evolved considerably but unraveling the extraordinary structural and functional complexity of the brain seems to be an unattainable goal, partly due to the fact that it is only possible to obtain an imprecise connection matrix of the brain. The reasons why reaching such a goal appears almost impossible to date is discussed here, together with suggestions of how we could overcome this anatomical problem by establishing new methodologies to study the brain and by promoting interdisciplinary collaboration. Generating a realistic computational model seems to be the solution rather than attempting to fully reconstruct the whole brain or a particular brain region.

No MeSH data available.


Related in: MedlinePlus

The central nervous system works as a whole. Schematic drawing by Barker (1899) to illustrate some of the multiple relationships between different parts of the central nervous system. Taken from DeFelipe (2014).
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Figure 1: The central nervous system works as a whole. Schematic drawing by Barker (1899) to illustrate some of the multiple relationships between different parts of the central nervous system. Taken from DeFelipe (2014).

Mentions: The words used by Nicolaus Steno to make his point could be taken as an introductory sentence to describe the magnitude of the problem in dealing with the anatomy of the brain, not only due to the complexity of its organization, but also because our knowledge of the brain is far from complete. The central nervous system works as a whole (Figure 1), and it is well established that the principles of structural design (spatial distribution, number and types of neurons, and synapses per volume, etc.) differ considerably in the different parts of the nervous system, as well as between species and strains. There is also considerable variation associated with age. Indeed, the early postnatal brain is structurally and functionally different from adolescent, young adult and older brain (Jacobs and Scheibel, 1993; Kolb et al., 1998; Marner et al., 2003; Stark et al., 2007; Feldmeyer and Radnikow, 2009; Workman et al., 2013; Luebke et al., 2015). Moreover, there is great interindividual variability in brain size, cortical thickness, number of cells, differences in dendritic trees, etc. (Jacobs et al., 1993; Uylings et al., 2005; Caspers et al., 2006; DeFelipe, 2011), as well as gender differences in multiple regions of the brain (Jacobs et al., 1993; Cahill, 2006; Alonso-Nanclares et al., 2008; Jazin and Cahill, 2010; Luders and Toga, 2010; Semaan and Kauffman, 2010). Therefore, the data obtained in one structure will not necessarily be applicable to another and thus, molecular, genetic and anatomical patterns must be examined separately in particular regions, species and strains, and for different ages and genders. When considering the magnitude of the problem further, solely from the neuroanatomical point of view, we must bear in mind the following considerations. Bota et al. (2003) suggests that in the mammalian central nervous system there are around 500–1000 different gray matter regions (e.g., the retina, dorsal lateral geniculate nucleus, and primary visual cortex); 2500–5000 neuron classes (e.g., retinal photoreceptors, bipolar cells, and ganglion cells); and 25,000–100,000 macroconnections between neuron classes (e.g., from retinal ganglion cells to dorsal lateral geniculate). The neuroanatomical information currently available in the literature provides data about 10% of all the possible long-range projections between the roughly 500 brain regions identified in the rat (Bota and Swanson, 2007). In addition, the vast majority of these studies only provide a qualitative vision of the projections. Thus, we are very far from obtaining a quantitative connectome map. In fact, we do not yet even have a complete map, let alone a quantitative one. For example, since the seminal study of Felleman and Van Essen (1991) of the cortical projections to areas V1, V2 and V4 in the primate cerebral cortex, there has been a major increase in the number of areas reported to project to these areas (see e.g., Markov et al., 2011). As we will see below, this problem is several orders of magnitude higher when we consider the information available using electron microscopy and indeed there is virtually no quantitative electron microscopy data.


The anatomical problem posed by brain complexity and size: a potential solution.

DeFelipe J - Front Neuroanat (2015)

The central nervous system works as a whole. Schematic drawing by Barker (1899) to illustrate some of the multiple relationships between different parts of the central nervous system. Taken from DeFelipe (2014).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4542575&req=5

Figure 1: The central nervous system works as a whole. Schematic drawing by Barker (1899) to illustrate some of the multiple relationships between different parts of the central nervous system. Taken from DeFelipe (2014).
Mentions: The words used by Nicolaus Steno to make his point could be taken as an introductory sentence to describe the magnitude of the problem in dealing with the anatomy of the brain, not only due to the complexity of its organization, but also because our knowledge of the brain is far from complete. The central nervous system works as a whole (Figure 1), and it is well established that the principles of structural design (spatial distribution, number and types of neurons, and synapses per volume, etc.) differ considerably in the different parts of the nervous system, as well as between species and strains. There is also considerable variation associated with age. Indeed, the early postnatal brain is structurally and functionally different from adolescent, young adult and older brain (Jacobs and Scheibel, 1993; Kolb et al., 1998; Marner et al., 2003; Stark et al., 2007; Feldmeyer and Radnikow, 2009; Workman et al., 2013; Luebke et al., 2015). Moreover, there is great interindividual variability in brain size, cortical thickness, number of cells, differences in dendritic trees, etc. (Jacobs et al., 1993; Uylings et al., 2005; Caspers et al., 2006; DeFelipe, 2011), as well as gender differences in multiple regions of the brain (Jacobs et al., 1993; Cahill, 2006; Alonso-Nanclares et al., 2008; Jazin and Cahill, 2010; Luders and Toga, 2010; Semaan and Kauffman, 2010). Therefore, the data obtained in one structure will not necessarily be applicable to another and thus, molecular, genetic and anatomical patterns must be examined separately in particular regions, species and strains, and for different ages and genders. When considering the magnitude of the problem further, solely from the neuroanatomical point of view, we must bear in mind the following considerations. Bota et al. (2003) suggests that in the mammalian central nervous system there are around 500–1000 different gray matter regions (e.g., the retina, dorsal lateral geniculate nucleus, and primary visual cortex); 2500–5000 neuron classes (e.g., retinal photoreceptors, bipolar cells, and ganglion cells); and 25,000–100,000 macroconnections between neuron classes (e.g., from retinal ganglion cells to dorsal lateral geniculate). The neuroanatomical information currently available in the literature provides data about 10% of all the possible long-range projections between the roughly 500 brain regions identified in the rat (Bota and Swanson, 2007). In addition, the vast majority of these studies only provide a qualitative vision of the projections. Thus, we are very far from obtaining a quantitative connectome map. In fact, we do not yet even have a complete map, let alone a quantitative one. For example, since the seminal study of Felleman and Van Essen (1991) of the cortical projections to areas V1, V2 and V4 in the primate cerebral cortex, there has been a major increase in the number of areas reported to project to these areas (see e.g., Markov et al., 2011). As we will see below, this problem is several orders of magnitude higher when we consider the information available using electron microscopy and indeed there is virtually no quantitative electron microscopy data.

Bottom Line: Over the years the field of neuroanatomy has evolved considerably but unraveling the extraordinary structural and functional complexity of the brain seems to be an unattainable goal, partly due to the fact that it is only possible to obtain an imprecise connection matrix of the brain.The reasons why reaching such a goal appears almost impossible to date is discussed here, together with suggestions of how we could overcome this anatomical problem by establishing new methodologies to study the brain and by promoting interdisciplinary collaboration.Generating a realistic computational model seems to be the solution rather than attempting to fully reconstruct the whole brain or a particular brain region.

View Article: PubMed Central - PubMed

Affiliation: Laboratorio Cajal de Circuitos Corticales (Centro de Tecnología Biomédica: UPM), Instituto Cajal (CSIC) and CIBERNED Madrid, Spain.

ABSTRACT
Over the years the field of neuroanatomy has evolved considerably but unraveling the extraordinary structural and functional complexity of the brain seems to be an unattainable goal, partly due to the fact that it is only possible to obtain an imprecise connection matrix of the brain. The reasons why reaching such a goal appears almost impossible to date is discussed here, together with suggestions of how we could overcome this anatomical problem by establishing new methodologies to study the brain and by promoting interdisciplinary collaboration. Generating a realistic computational model seems to be the solution rather than attempting to fully reconstruct the whole brain or a particular brain region.

No MeSH data available.


Related in: MedlinePlus