DSCAM differentially modulates pre- and postsynaptic structural and functional central connectivity during visual system wiring
Abstract Background Proper patterning of dendritic and axonal arbors is a critical step in the formation of functional neuronal circuits. Developing circuits rely on an array of molecular cues to shape arbor morphology, but the underlying mechanisms guiding the structural formation and interconnecti...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-09-01
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| Series: | Neural Development |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13064-018-0118-5 |
| _version_ | 1828413173554741248 |
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| author | Rommel A. Santos Ariel J. C. Fuertes Ginger Short Kevin C. Donohue Hanjuan Shao Julian Quintanilla Parinaz Malakzadeh Susana Cohen-Cory |
| author_facet | Rommel A. Santos Ariel J. C. Fuertes Ginger Short Kevin C. Donohue Hanjuan Shao Julian Quintanilla Parinaz Malakzadeh Susana Cohen-Cory |
| author_sort | Rommel A. Santos |
| collection | DOAJ |
| description | Abstract Background Proper patterning of dendritic and axonal arbors is a critical step in the formation of functional neuronal circuits. Developing circuits rely on an array of molecular cues to shape arbor morphology, but the underlying mechanisms guiding the structural formation and interconnectivity of pre- and postsynaptic arbors in real time remain unclear. Here we explore how Down syndrome cell adhesion molecule (DSCAM) differentially shapes the dendritic morphology of central neurons and their presynaptic retinal ganglion cell (RGC) axons in the developing vertebrate visual system. Methods The cell-autonomous role of DSCAM, in tectal neurons and in RGCs, was examined using targeted single-cell knockdown and overexpression approaches in developing Xenopus laevis tadpoles. Axonal arbors of RGCs and dendritic arbors of tectal neurons were visualized using real-time in vivo confocal microscopy imaging over the course of 3 days. Results In the Xenopus visual system, DSCAM immunoreactivity is present in RGCs, cells in the optic tectum and the tectal neuropil at the time retinotectal synaptic connections are made. Downregulating DSCAM in tectal neurons significantly increased dendritic growth and branching rates while inducing dendrites to take on tortuous paths. Overexpression of DSCAM, in contrast, reduced dendritic branching and growth rate. Functional deficits mediated by tectal DSCAM knockdown were examined using visually guided behavioral assays in swimming tadpoles, revealing irregular behavioral responses to visual stimulus. Functional deficits in visual behavior also corresponded with changes in VGLUT/VGAT expression, markers of excitatory and inhibitory transmission, in the tectum. Conversely, single-cell DSCAM knockdown in the retina revealed that RGC axon arborization at the target is influenced by DSCAM, where axons grew at a slower rate and remained relatively simple. In the retina, dendritic arbors of RGCs were not affected by the reduction of DSCAM expression. Conclusions Together, our observations implicate DSCAM in the control of both pre- and postsynaptic structural and functional connectivity in the developing retinotectal circuit, where it primarily acts as a neuronal brake to limit and guide postsynaptic dendrite growth of tectal neurons while it also facilitates arborization of presynaptic RGC axons cell autonomously. |
| first_indexed | 2024-12-10T13:02:56Z |
| format | Article |
| id | doaj.art-f727e72386684573bff81905766e7cfc |
| institution | Directory Open Access Journal |
| issn | 1749-8104 |
| language | English |
| last_indexed | 2024-12-10T13:02:56Z |
| publishDate | 2018-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Neural Development |
| spelling | doaj.art-f727e72386684573bff81905766e7cfc2022-12-22T01:47:55ZengBMCNeural Development1749-81042018-09-0113111910.1186/s13064-018-0118-5DSCAM differentially modulates pre- and postsynaptic structural and functional central connectivity during visual system wiringRommel A. Santos0Ariel J. C. Fuertes1Ginger Short2Kevin C. Donohue3Hanjuan Shao4Julian Quintanilla5Parinaz Malakzadeh6Susana Cohen-Cory7Department of Neurobiology and Behavior, University of California, IrvineDepartment of Neurobiology and Behavior, University of California, IrvineDepartment of Neurobiology and Behavior, University of California, IrvineDepartment of Neurobiology and Behavior, University of California, IrvineDepartment of Neurobiology and Behavior, University of California, IrvineDepartment of Neurobiology and Behavior, University of California, IrvineDepartment of Neurobiology and Behavior, University of California, IrvineDepartment of Neurobiology and Behavior, University of California, IrvineAbstract Background Proper patterning of dendritic and axonal arbors is a critical step in the formation of functional neuronal circuits. Developing circuits rely on an array of molecular cues to shape arbor morphology, but the underlying mechanisms guiding the structural formation and interconnectivity of pre- and postsynaptic arbors in real time remain unclear. Here we explore how Down syndrome cell adhesion molecule (DSCAM) differentially shapes the dendritic morphology of central neurons and their presynaptic retinal ganglion cell (RGC) axons in the developing vertebrate visual system. Methods The cell-autonomous role of DSCAM, in tectal neurons and in RGCs, was examined using targeted single-cell knockdown and overexpression approaches in developing Xenopus laevis tadpoles. Axonal arbors of RGCs and dendritic arbors of tectal neurons were visualized using real-time in vivo confocal microscopy imaging over the course of 3 days. Results In the Xenopus visual system, DSCAM immunoreactivity is present in RGCs, cells in the optic tectum and the tectal neuropil at the time retinotectal synaptic connections are made. Downregulating DSCAM in tectal neurons significantly increased dendritic growth and branching rates while inducing dendrites to take on tortuous paths. Overexpression of DSCAM, in contrast, reduced dendritic branching and growth rate. Functional deficits mediated by tectal DSCAM knockdown were examined using visually guided behavioral assays in swimming tadpoles, revealing irregular behavioral responses to visual stimulus. Functional deficits in visual behavior also corresponded with changes in VGLUT/VGAT expression, markers of excitatory and inhibitory transmission, in the tectum. Conversely, single-cell DSCAM knockdown in the retina revealed that RGC axon arborization at the target is influenced by DSCAM, where axons grew at a slower rate and remained relatively simple. In the retina, dendritic arbors of RGCs were not affected by the reduction of DSCAM expression. Conclusions Together, our observations implicate DSCAM in the control of both pre- and postsynaptic structural and functional connectivity in the developing retinotectal circuit, where it primarily acts as a neuronal brake to limit and guide postsynaptic dendrite growth of tectal neurons while it also facilitates arborization of presynaptic RGC axons cell autonomously.http://link.springer.com/article/10.1186/s13064-018-0118-5DSCAMIn vivo imagingDendritogenesisAxon branchingOptic tectumRetina |
| spellingShingle | Rommel A. Santos Ariel J. C. Fuertes Ginger Short Kevin C. Donohue Hanjuan Shao Julian Quintanilla Parinaz Malakzadeh Susana Cohen-Cory DSCAM differentially modulates pre- and postsynaptic structural and functional central connectivity during visual system wiring Neural Development DSCAM In vivo imaging Dendritogenesis Axon branching Optic tectum Retina |
| title | DSCAM differentially modulates pre- and postsynaptic structural and functional central connectivity during visual system wiring |
| title_full | DSCAM differentially modulates pre- and postsynaptic structural and functional central connectivity during visual system wiring |
| title_fullStr | DSCAM differentially modulates pre- and postsynaptic structural and functional central connectivity during visual system wiring |
| title_full_unstemmed | DSCAM differentially modulates pre- and postsynaptic structural and functional central connectivity during visual system wiring |
| title_short | DSCAM differentially modulates pre- and postsynaptic structural and functional central connectivity during visual system wiring |
| title_sort | dscam differentially modulates pre and postsynaptic structural and functional central connectivity during visual system wiring |
| topic | DSCAM In vivo imaging Dendritogenesis Axon branching Optic tectum Retina |
| url | http://link.springer.com/article/10.1186/s13064-018-0118-5 |
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