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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.


Camera lucida reconstruction of two motor thalamocortical axons in the rat labeled with viral vectors. Axon fibers of IZ neurons (inhibitory afferent-dominant zone of the ventral anterior-ventral lateral motor thalamic nuclei [VA-VL complex]) were widely distributed in motor-associated areas and neostriatum (A). Of cerebral cortical layers, layer I was most intensely innervated by the axon fibers of IZ neurons (B–D). In contrast, axon fibers of EZ neurons (excitatory subcortical afferent-dominant zone of the VA-VL complex) were found only in motor-associated areas (E) and distributed mainly in cortical layers II–V (F,G). Panels (D,G) are representative planes, in which the results of 10 serial sections were superimposed onto a parasagittal plane of the fifth section. Other abbreviations: FL, forelimb region of primary somatosensory-motor area; HL, hindlimb region of primary somatosensory-motor area; M1, primary motor area; M2, secondary motor area; S1, primary somatosensory area. Courtesy of Takeshi Kaneko. Figure and legend taken from Kuramoto et al. (2009).
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Figure 6: Camera lucida reconstruction of two motor thalamocortical axons in the rat labeled with viral vectors. Axon fibers of IZ neurons (inhibitory afferent-dominant zone of the ventral anterior-ventral lateral motor thalamic nuclei [VA-VL complex]) were widely distributed in motor-associated areas and neostriatum (A). Of cerebral cortical layers, layer I was most intensely innervated by the axon fibers of IZ neurons (B–D). In contrast, axon fibers of EZ neurons (excitatory subcortical afferent-dominant zone of the VA-VL complex) were found only in motor-associated areas (E) and distributed mainly in cortical layers II–V (F,G). Panels (D,G) are representative planes, in which the results of 10 serial sections were superimposed onto a parasagittal plane of the fifth section. Other abbreviations: FL, forelimb region of primary somatosensory-motor area; HL, hindlimb region of primary somatosensory-motor area; M1, primary motor area; M2, secondary motor area; S1, primary somatosensory area. Courtesy of Takeshi Kaneko. Figure and legend taken from Kuramoto et al. (2009).

Mentions: If we were to follow the extrinsic axons entering the minicolumn that establish synapses with postsynaptic elements of the minicolumn, like motor thalamocortical axons in the rat (Kuramoto et al., 2009) for instance, we would have to face a similar difficulty due to the complexity and widespread axonal arborizations of these neurons (Figure 6). This problem would be even greater if we were to follow an extrinsic axon originating in the basal forebrain. For example, the studies of Wu et al. (2014)—using genetically-directed sparse labeling to examine the full morphologies of individual basal forebrain cholinergic neurons in the mouse—have shown that individual arbors innervate multiple cortical columns, and have >1000 branch points and total axon lengths of up to 50 cm. These authors have also estimated that basal forebrain cholinergic neurons in humans have a mean axon length of ~100 meters. Furthermore, the axons of most cortical neurons (i.e., pyramidal cells) give rise to local axonal arborizations (near the cell body of origin) but the number of axonal synaptic boutons is relatively low (in the order of a few hundreds; see e.g., DeFelipe et al., 1986; Figure 7). Thus, the majority of other synapses within the minicolumn are of extrinsic origin (i.e., axon terminals coming from neurons with a distant origin, like cortico-cortical neurons, thalamo-cortical neurons, etc.). Table 1 outlines the feasibility and non-feasibility of obtaining some critical quantitative anatomical data of the minicolumn that is relevant for connectomics and models.


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

DeFelipe J - Front Neuroanat (2015)

Camera lucida reconstruction of two motor thalamocortical axons in the rat labeled with viral vectors. Axon fibers of IZ neurons (inhibitory afferent-dominant zone of the ventral anterior-ventral lateral motor thalamic nuclei [VA-VL complex]) were widely distributed in motor-associated areas and neostriatum (A). Of cerebral cortical layers, layer I was most intensely innervated by the axon fibers of IZ neurons (B–D). In contrast, axon fibers of EZ neurons (excitatory subcortical afferent-dominant zone of the VA-VL complex) were found only in motor-associated areas (E) and distributed mainly in cortical layers II–V (F,G). Panels (D,G) are representative planes, in which the results of 10 serial sections were superimposed onto a parasagittal plane of the fifth section. Other abbreviations: FL, forelimb region of primary somatosensory-motor area; HL, hindlimb region of primary somatosensory-motor area; M1, primary motor area; M2, secondary motor area; S1, primary somatosensory area. Courtesy of Takeshi Kaneko. Figure and legend taken from Kuramoto et al. (2009).
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Figure 6: Camera lucida reconstruction of two motor thalamocortical axons in the rat labeled with viral vectors. Axon fibers of IZ neurons (inhibitory afferent-dominant zone of the ventral anterior-ventral lateral motor thalamic nuclei [VA-VL complex]) were widely distributed in motor-associated areas and neostriatum (A). Of cerebral cortical layers, layer I was most intensely innervated by the axon fibers of IZ neurons (B–D). In contrast, axon fibers of EZ neurons (excitatory subcortical afferent-dominant zone of the VA-VL complex) were found only in motor-associated areas (E) and distributed mainly in cortical layers II–V (F,G). Panels (D,G) are representative planes, in which the results of 10 serial sections were superimposed onto a parasagittal plane of the fifth section. Other abbreviations: FL, forelimb region of primary somatosensory-motor area; HL, hindlimb region of primary somatosensory-motor area; M1, primary motor area; M2, secondary motor area; S1, primary somatosensory area. Courtesy of Takeshi Kaneko. Figure and legend taken from Kuramoto et al. (2009).
Mentions: If we were to follow the extrinsic axons entering the minicolumn that establish synapses with postsynaptic elements of the minicolumn, like motor thalamocortical axons in the rat (Kuramoto et al., 2009) for instance, we would have to face a similar difficulty due to the complexity and widespread axonal arborizations of these neurons (Figure 6). This problem would be even greater if we were to follow an extrinsic axon originating in the basal forebrain. For example, the studies of Wu et al. (2014)—using genetically-directed sparse labeling to examine the full morphologies of individual basal forebrain cholinergic neurons in the mouse—have shown that individual arbors innervate multiple cortical columns, and have >1000 branch points and total axon lengths of up to 50 cm. These authors have also estimated that basal forebrain cholinergic neurons in humans have a mean axon length of ~100 meters. Furthermore, the axons of most cortical neurons (i.e., pyramidal cells) give rise to local axonal arborizations (near the cell body of origin) but the number of axonal synaptic boutons is relatively low (in the order of a few hundreds; see e.g., DeFelipe et al., 1986; Figure 7). Thus, the majority of other synapses within the minicolumn are of extrinsic origin (i.e., axon terminals coming from neurons with a distant origin, like cortico-cortical neurons, thalamo-cortical neurons, etc.). Table 1 outlines the feasibility and non-feasibility of obtaining some critical quantitative anatomical data of the minicolumn that is relevant for connectomics and models.

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.