Developmental Dynamics of the Mouse Retinocollicular Projection: A Quantitative Characterisation

Daniel Lyngholm

Research output: ThesisDoctoral Thesis

Abstract

Development of retinotopy is an area of longstanding investigation, and it is clear that this development is influenced by both molecular and activity-based cues. The interaction between these different cues, however, is unclear: conventionally molecular guidance cues set the basic topography, which is then refined by activity-based mechanisms. A number of computational models have investigated this interaction. However, due to the limited availability of quantitative data it has not been possible to test whether the models can account for the precise developmental sequence of retinotopic map formation. This thesis provides such quantitative anatomical data about the spatiotemporal sequence of development of precision in the retinocollicular projection in the mouse. This characterisation has been done by utilising retrograde transport of fluorescent microspheres administered by discrete injections into the SC and recovered from retinal flat-mounts. To enable quantification of topographic precision, retinae are standardised using an algorithm that permits retinal outlines to be stitched back together into a sphere and cell locations plotted in spherical coordinates, which enables mapping across multiple animals and facilitates comparison between different age-points, genotypes and potentially different species. The anatomical description reveals the precise dynamics of retinocollicular projection refinement, as projection refines from having almost no precision along the SC AP axis at birth to having topographically accurate, albeit imprecise, but symmetrical precision by the end of the first postnatal week. The data, moreover, reveals that the period of refinement extends significant beyond the first postnatal week and refinement is even seen after the third postnatal week.
It is also found that the early refinement is crucially dependent on specific patterns of spontaneous retinal activity, since altering the activity-patterns by removing the nAChR-|32 subunit completely disrupts the refinement normally seen in the first postnatal week. Furthermore, it is found that refinement does occur in these animals after the first postnatal week, but it does not rescue the phenotype.
LanguageEnglish
QualificationPhD
Awarding Institution
  • King's College London
Supervisors/Advisors
  • Thompson, Ian D, Supervisor, External person
  • Hindges, Robert, Supervisor, External person
Place of PublicationLondon
Publication statusPublished - 2012

Fingerprint

Cues
Microspheres
Retina
Genotype
Parturition
Phenotype
Injections

Keywords

  • mouse retinocollicular projection
  • retinal activity

Cite this

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title = "Developmental Dynamics of the Mouse Retinocollicular Projection: A Quantitative Characterisation",
abstract = "Development of retinotopy is an area of longstanding investigation, and it is clear that this development is influenced by both molecular and activity-based cues. The interaction between these different cues, however, is unclear: conventionally molecular guidance cues set the basic topography, which is then refined by activity-based mechanisms. A number of computational models have investigated this interaction. However, due to the limited availability of quantitative data it has not been possible to test whether the models can account for the precise developmental sequence of retinotopic map formation. This thesis provides such quantitative anatomical data about the spatiotemporal sequence of development of precision in the retinocollicular projection in the mouse. This characterisation has been done by utilising retrograde transport of fluorescent microspheres administered by discrete injections into the SC and recovered from retinal flat-mounts. To enable quantification of topographic precision, retinae are standardised using an algorithm that permits retinal outlines to be stitched back together into a sphere and cell locations plotted in spherical coordinates, which enables mapping across multiple animals and facilitates comparison between different age-points, genotypes and potentially different species. The anatomical description reveals the precise dynamics of retinocollicular projection refinement, as projection refines from having almost no precision along the SC AP axis at birth to having topographically accurate, albeit imprecise, but symmetrical precision by the end of the first postnatal week. The data, moreover, reveals that the period of refinement extends significant beyond the first postnatal week and refinement is even seen after the third postnatal week.It is also found that the early refinement is crucially dependent on specific patterns of spontaneous retinal activity, since altering the activity-patterns by removing the nAChR-|32 subunit completely disrupts the refinement normally seen in the first postnatal week. Furthermore, it is found that refinement does occur in these animals after the first postnatal week, but it does not rescue the phenotype.",
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Developmental Dynamics of the Mouse Retinocollicular Projection: A Quantitative Characterisation. / Lyngholm, Daniel.

London, 2012.

Research output: ThesisDoctoral Thesis

TY - THES

T1 - Developmental Dynamics of the Mouse Retinocollicular Projection: A Quantitative Characterisation

AU - Lyngholm, Daniel

PY - 2012

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N2 - Development of retinotopy is an area of longstanding investigation, and it is clear that this development is influenced by both molecular and activity-based cues. The interaction between these different cues, however, is unclear: conventionally molecular guidance cues set the basic topography, which is then refined by activity-based mechanisms. A number of computational models have investigated this interaction. However, due to the limited availability of quantitative data it has not been possible to test whether the models can account for the precise developmental sequence of retinotopic map formation. This thesis provides such quantitative anatomical data about the spatiotemporal sequence of development of precision in the retinocollicular projection in the mouse. This characterisation has been done by utilising retrograde transport of fluorescent microspheres administered by discrete injections into the SC and recovered from retinal flat-mounts. To enable quantification of topographic precision, retinae are standardised using an algorithm that permits retinal outlines to be stitched back together into a sphere and cell locations plotted in spherical coordinates, which enables mapping across multiple animals and facilitates comparison between different age-points, genotypes and potentially different species. The anatomical description reveals the precise dynamics of retinocollicular projection refinement, as projection refines from having almost no precision along the SC AP axis at birth to having topographically accurate, albeit imprecise, but symmetrical precision by the end of the first postnatal week. The data, moreover, reveals that the period of refinement extends significant beyond the first postnatal week and refinement is even seen after the third postnatal week.It is also found that the early refinement is crucially dependent on specific patterns of spontaneous retinal activity, since altering the activity-patterns by removing the nAChR-|32 subunit completely disrupts the refinement normally seen in the first postnatal week. Furthermore, it is found that refinement does occur in these animals after the first postnatal week, but it does not rescue the phenotype.

AB - Development of retinotopy is an area of longstanding investigation, and it is clear that this development is influenced by both molecular and activity-based cues. The interaction between these different cues, however, is unclear: conventionally molecular guidance cues set the basic topography, which is then refined by activity-based mechanisms. A number of computational models have investigated this interaction. However, due to the limited availability of quantitative data it has not been possible to test whether the models can account for the precise developmental sequence of retinotopic map formation. This thesis provides such quantitative anatomical data about the spatiotemporal sequence of development of precision in the retinocollicular projection in the mouse. This characterisation has been done by utilising retrograde transport of fluorescent microspheres administered by discrete injections into the SC and recovered from retinal flat-mounts. To enable quantification of topographic precision, retinae are standardised using an algorithm that permits retinal outlines to be stitched back together into a sphere and cell locations plotted in spherical coordinates, which enables mapping across multiple animals and facilitates comparison between different age-points, genotypes and potentially different species. The anatomical description reveals the precise dynamics of retinocollicular projection refinement, as projection refines from having almost no precision along the SC AP axis at birth to having topographically accurate, albeit imprecise, but symmetrical precision by the end of the first postnatal week. The data, moreover, reveals that the period of refinement extends significant beyond the first postnatal week and refinement is even seen after the third postnatal week.It is also found that the early refinement is crucially dependent on specific patterns of spontaneous retinal activity, since altering the activity-patterns by removing the nAChR-|32 subunit completely disrupts the refinement normally seen in the first postnatal week. Furthermore, it is found that refinement does occur in these animals after the first postnatal week, but it does not rescue the phenotype.

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KW - retinal activity

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M3 - Doctoral Thesis

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