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DSCAM differentially modulates pre- and postsynaptic structural and functional central connectivity during visual system wiring

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...

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Autores principales: Santos, Rommel A., Fuertes, Ariel J. C., Short, Ginger, Donohue, Kevin C., Shao, Hanjuan, Quintanilla, Julian, Malakzadeh, Parinaz, Cohen-Cory, Susana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138929/
https://www.ncbi.nlm.nih.gov/pubmed/30219101
http://dx.doi.org/10.1186/s13064-018-0118-5
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author Santos, Rommel A.
Fuertes, Ariel J. C.
Short, Ginger
Donohue, Kevin C.
Shao, Hanjuan
Quintanilla, Julian
Malakzadeh, Parinaz
Cohen-Cory, Susana
author_facet Santos, Rommel A.
Fuertes, Ariel J. C.
Short, Ginger
Donohue, Kevin C.
Shao, Hanjuan
Quintanilla, Julian
Malakzadeh, Parinaz
Cohen-Cory, Susana
author_sort Santos, Rommel A.
collection PubMed
description 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.
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spelling pubmed-61389292018-09-20 DSCAM differentially modulates pre- and postsynaptic structural and functional central connectivity during visual system wiring Santos, Rommel A. Fuertes, Ariel J. C. Short, Ginger Donohue, Kevin C. Shao, Hanjuan Quintanilla, Julian Malakzadeh, Parinaz Cohen-Cory, Susana Neural Dev Research Article 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. BioMed Central 2018-09-15 /pmc/articles/PMC6138929/ /pubmed/30219101 http://dx.doi.org/10.1186/s13064-018-0118-5 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Santos, Rommel A.
Fuertes, Ariel J. C.
Short, Ginger
Donohue, Kevin C.
Shao, Hanjuan
Quintanilla, Julian
Malakzadeh, Parinaz
Cohen-Cory, Susana
DSCAM differentially modulates pre- and postsynaptic structural and functional central connectivity during visual system wiring
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 Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138929/
https://www.ncbi.nlm.nih.gov/pubmed/30219101
http://dx.doi.org/10.1186/s13064-018-0118-5
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