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Diadem X: automated 4 dimensional analysis of morphological data.

He HY, Cline HT - Neuroinformatics (2011)

View Article: PubMed Central - PubMed

Affiliation: The Scripps Research Institute, La Jolla, CA 92037, USA.

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The development of multi-photon imaging technique has greatly facilitated in vivo time-lapse imaging and enables comparison of the fine morphological structures of individual neurons over time... Despite the fact that 4D data acquisition has become easier and can be applied to a variety of brain tissues, both in vivo and in tissue slices, the analysis of these 4D data remains extremely laborious and painstaking... Although the mechanisms underlying this widely observed effect of TTX treatment are still unclear, this was the first demonstration that neuronal activity affected the growth and structure of individual neurons... Subsequently Antonini and Stryker conducted heroic experiments (Fig.  1) which demonstrated that the morphology of individual geniculocortical axons changes over periods of days in response to decreased visual experience. 7 Specifically, by comparing populations of neurons from animals treated with monocular deprivation, they found that geniculocortical axons carrying information in the open eye pathway elaborated more complex axon arbors than axons in the deprived-eye pathway. 8 These experiments were important because they demonstrated that sensory input activity governed the elaboration of neuronal axons and that the gross re-organization of ocular dominance columns in monocularly-deprived animals seen using radioactive tracers reported a population-level change in neuronal structure, rather than, for instance, a change in the distribution of axons within layer 4 of visual cortex... It is important to point out that these conclusions were generated by comparing populations of neurons from animals at different stages and treated with different visual stimulation or deprivation paradigms, so that specific information about cellular mechanisms governing elaboration or regression of axon arbor development could not be determined... Many studies have documented the invasion and development of axon arbors by comparing samples across different developmental timepoints. 9 In parallel, other studies demonstrated an increase followed by a gradual decrease in synapse density. 10 Together these studies suggested a model in which axon arbors go through a period of exuberant elaboration and excess synaptogenesis followed by an elimination phase, in which both synapses and axon branches were pruned... As described by Hua and Smith,11 this classical model of sequential axon arbor elaboration and pruning is not borne out by time-lapse in vivo imaging of developing retinotectal axons in Xenopus frog tadpoles and Zebrafish. 1213 Rather, branch addition and synaptogenesis are concurrent with branch retraction and synapse elimination for both axons and dendrites, as suggested by light microscopy time-lapse data14 and demonstrated more conclusively by combining in vivo time-lapse imaging with subsequent serial section electron microscopy. 15 Importantly, the final structure of the axon is indistinguishable (Fig.  2), and these fundamental differences in the cellular mechanisms, and therefore the molecular/genetic/signaling events underlying arbor development, would only be recognized by time-lapse in vivo imaging data... This serves as but one example of the essential need for in vivo time-lapse imaging data for accurate identification of mechanisms governing brain development, circuit plasticity and neurological diseases... The development of multi-photon imaging techniques has greatly facilitated in vivo time-lapse imaging, which enables comparison of the fine morphological structures of individual neurons over time... Despite the fact that 4D data acquisition has become easier and can be applied to a variety of brain tissues, both in vivo and in tissue slices, the analysis of these 4D data remains extremely laborious and painstaking... A second technical issue is the identification of persistent and new structures (branch tips, boutons, spines) in sequential images... Despite the fact that comparison of 3 dimensional data sets remains a significant challenge, recent progress in a number of labs suggests that semi-automated analysis of time-lapse images of neuronal structures is a tractable problem within the near future... Such automation will have a significant impact on the ability to assess developmental, plasticity-induced, regressive or therapeutic changes in nervous system structure and will follow smoothly from the advances seen as a result of the Diadem Challenge.

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a Ocular dominance plasticity in non-human primates following monocular deprivation, according to autoradiographic visualization of radiolabel injected into one eye. Adapted from Hubel, Levay and Weisell, 1977. b Examples of geniculocortical axon arbor structures from cats with monocular deprivation. Axons from the closed eye and open eye pathways are shown. Adapted from Antonini and Stryker, 1993
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Fig1: a Ocular dominance plasticity in non-human primates following monocular deprivation, according to autoradiographic visualization of radiolabel injected into one eye. Adapted from Hubel, Levay and Weisell, 1977. b Examples of geniculocortical axon arbor structures from cats with monocular deprivation. Axons from the closed eye and open eye pathways are shown. Adapted from Antonini and Stryker, 1993

Mentions: Classical experiments have demonstrated that neuronal structure changes in response to sensory experience. For instance, using both electrophysiological and anatomical methods, Hubel, Weisel, Levay and colleagues showed ocular dominance column plasticity in non-human primates (Fig. 1) and other mammals with front-facing eyes.3 Using the three-eyed frog experimental system,4 Reh and Constantine-Paton showed that blockade of action potential activity with tetrodotoxin (TTX) desegregated ocular dominance columns,5,6 a result that was subsequently reproduced in mammals.6 These results indicated that action potential activity in sensory inputs was an important element in organizing central projections. Reh and Constantine-Paton made another important observation: they reported that TTX treatment increased the elaboration of retinal axon arbors.5 Although the mechanisms underlying this widely observed effect of TTX treatment are still unclear, this was the first demonstration that neuronal activity affected the growth and structure of individual neurons. Subsequently Antonini and Stryker conducted heroic experiments (Fig. 1) which demonstrated that the morphology of individual geniculocortical axons changes over periods of days in response to decreased visual experience.7 Specifically, by comparing populations of neurons from animals treated with monocular deprivation, they found that geniculocortical axons carrying information in the open eye pathway elaborated more complex axon arbors than axons in the deprived-eye pathway.8 These experiments were important because they demonstrated that sensory input activity governed the elaboration of neuronal axons and that the gross re-organization of ocular dominance columns in monocularly-deprived animals seen using radioactive tracers reported a population-level change in neuronal structure, rather than, for instance, a change in the distribution of axons within layer 4 of visual cortex. It is important to point out that these conclusions were generated by comparing populations of neurons from animals at different stages and treated with different visual stimulation or deprivation paradigms, so that specific information about cellular mechanisms governing elaboration or regression of axon arbor development could not be determined.Fig. 1


Diadem X: automated 4 dimensional analysis of morphological data.

He HY, Cline HT - Neuroinformatics (2011)

a Ocular dominance plasticity in non-human primates following monocular deprivation, according to autoradiographic visualization of radiolabel injected into one eye. Adapted from Hubel, Levay and Weisell, 1977. b Examples of geniculocortical axon arbor structures from cats with monocular deprivation. Axons from the closed eye and open eye pathways are shown. Adapted from Antonini and Stryker, 1993
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3104138&req=5

Fig1: a Ocular dominance plasticity in non-human primates following monocular deprivation, according to autoradiographic visualization of radiolabel injected into one eye. Adapted from Hubel, Levay and Weisell, 1977. b Examples of geniculocortical axon arbor structures from cats with monocular deprivation. Axons from the closed eye and open eye pathways are shown. Adapted from Antonini and Stryker, 1993
Mentions: Classical experiments have demonstrated that neuronal structure changes in response to sensory experience. For instance, using both electrophysiological and anatomical methods, Hubel, Weisel, Levay and colleagues showed ocular dominance column plasticity in non-human primates (Fig. 1) and other mammals with front-facing eyes.3 Using the three-eyed frog experimental system,4 Reh and Constantine-Paton showed that blockade of action potential activity with tetrodotoxin (TTX) desegregated ocular dominance columns,5,6 a result that was subsequently reproduced in mammals.6 These results indicated that action potential activity in sensory inputs was an important element in organizing central projections. Reh and Constantine-Paton made another important observation: they reported that TTX treatment increased the elaboration of retinal axon arbors.5 Although the mechanisms underlying this widely observed effect of TTX treatment are still unclear, this was the first demonstration that neuronal activity affected the growth and structure of individual neurons. Subsequently Antonini and Stryker conducted heroic experiments (Fig. 1) which demonstrated that the morphology of individual geniculocortical axons changes over periods of days in response to decreased visual experience.7 Specifically, by comparing populations of neurons from animals treated with monocular deprivation, they found that geniculocortical axons carrying information in the open eye pathway elaborated more complex axon arbors than axons in the deprived-eye pathway.8 These experiments were important because they demonstrated that sensory input activity governed the elaboration of neuronal axons and that the gross re-organization of ocular dominance columns in monocularly-deprived animals seen using radioactive tracers reported a population-level change in neuronal structure, rather than, for instance, a change in the distribution of axons within layer 4 of visual cortex. It is important to point out that these conclusions were generated by comparing populations of neurons from animals at different stages and treated with different visual stimulation or deprivation paradigms, so that specific information about cellular mechanisms governing elaboration or regression of axon arbor development could not be determined.Fig. 1

View Article: PubMed Central - PubMed

Affiliation: The Scripps Research Institute, La Jolla, CA 92037, USA.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

The development of multi-photon imaging technique has greatly facilitated in vivo time-lapse imaging and enables comparison of the fine morphological structures of individual neurons over time... Despite the fact that 4D data acquisition has become easier and can be applied to a variety of brain tissues, both in vivo and in tissue slices, the analysis of these 4D data remains extremely laborious and painstaking... Although the mechanisms underlying this widely observed effect of TTX treatment are still unclear, this was the first demonstration that neuronal activity affected the growth and structure of individual neurons... Subsequently Antonini and Stryker conducted heroic experiments (Fig.  1) which demonstrated that the morphology of individual geniculocortical axons changes over periods of days in response to decreased visual experience. 7 Specifically, by comparing populations of neurons from animals treated with monocular deprivation, they found that geniculocortical axons carrying information in the open eye pathway elaborated more complex axon arbors than axons in the deprived-eye pathway. 8 These experiments were important because they demonstrated that sensory input activity governed the elaboration of neuronal axons and that the gross re-organization of ocular dominance columns in monocularly-deprived animals seen using radioactive tracers reported a population-level change in neuronal structure, rather than, for instance, a change in the distribution of axons within layer 4 of visual cortex... It is important to point out that these conclusions were generated by comparing populations of neurons from animals at different stages and treated with different visual stimulation or deprivation paradigms, so that specific information about cellular mechanisms governing elaboration or regression of axon arbor development could not be determined... Many studies have documented the invasion and development of axon arbors by comparing samples across different developmental timepoints. 9 In parallel, other studies demonstrated an increase followed by a gradual decrease in synapse density. 10 Together these studies suggested a model in which axon arbors go through a period of exuberant elaboration and excess synaptogenesis followed by an elimination phase, in which both synapses and axon branches were pruned... As described by Hua and Smith,11 this classical model of sequential axon arbor elaboration and pruning is not borne out by time-lapse in vivo imaging of developing retinotectal axons in Xenopus frog tadpoles and Zebrafish. 1213 Rather, branch addition and synaptogenesis are concurrent with branch retraction and synapse elimination for both axons and dendrites, as suggested by light microscopy time-lapse data14 and demonstrated more conclusively by combining in vivo time-lapse imaging with subsequent serial section electron microscopy. 15 Importantly, the final structure of the axon is indistinguishable (Fig.  2), and these fundamental differences in the cellular mechanisms, and therefore the molecular/genetic/signaling events underlying arbor development, would only be recognized by time-lapse in vivo imaging data... This serves as but one example of the essential need for in vivo time-lapse imaging data for accurate identification of mechanisms governing brain development, circuit plasticity and neurological diseases... The development of multi-photon imaging techniques has greatly facilitated in vivo time-lapse imaging, which enables comparison of the fine morphological structures of individual neurons over time... Despite the fact that 4D data acquisition has become easier and can be applied to a variety of brain tissues, both in vivo and in tissue slices, the analysis of these 4D data remains extremely laborious and painstaking... A second technical issue is the identification of persistent and new structures (branch tips, boutons, spines) in sequential images... Despite the fact that comparison of 3 dimensional data sets remains a significant challenge, recent progress in a number of labs suggests that semi-automated analysis of time-lapse images of neuronal structures is a tractable problem within the near future... Such automation will have a significant impact on the ability to assess developmental, plasticity-induced, regressive or therapeutic changes in nervous system structure and will follow smoothly from the advances seen as a result of the Diadem Challenge.

Show MeSH
Related in: MedlinePlus