Neurotransmitter-mediated activity spatially controls neuronal migration in the zebrafish cerebellum
Neuronal migration during embryonic development contributes to functional brain circuitry. Many neurons migrate in morphologically distinct stages that coincide with differentiation, requiring tight spatial regulation. It had been proposed that neurotransmitter-mediated activity could exert this con...
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| Veröffentlicht in: | PLoS biology 2018-01, Vol.16 (1), p.e2002226-e2002226 |
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| creator | Theisen, Ulrike Hennig, Christian Ring, Tobias Schnabel, Ralf Köster, Reinhard W |
| description | Neuronal migration during embryonic development contributes to functional brain circuitry. Many neurons migrate in morphologically distinct stages that coincide with differentiation, requiring tight spatial regulation. It had been proposed that neurotransmitter-mediated activity could exert this control. Here, we demonstrate that intracellular calcium transients occur in cerebellar neurons of zebrafish embryos during migration. We show that depolarization increases and hyperpolarization reduces the speed of tegmental hindbrain neurons using optogenetic tools and advanced track analysis optimized for in vivo migration. Finally, we introduce a compound screening assay to identify acetylcholine (ACh), glutamate, and glycine as regulators of migration, which act regionally along the neurons' route. We summarize our findings in a model describing how different neurotransmitters spatially interact to control neuronal migration. The high evolutionary conservation of the cerebellum and hindbrain makes it likely that polarization state-driven motility constitutes an important principle in building a functional brain. |
| doi_str_mv | 10.1371/journal.pbio.2002226 |
| format | Article |
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Many neurons migrate in morphologically distinct stages that coincide with differentiation, requiring tight spatial regulation. It had been proposed that neurotransmitter-mediated activity could exert this control. Here, we demonstrate that intracellular calcium transients occur in cerebellar neurons of zebrafish embryos during migration. We show that depolarization increases and hyperpolarization reduces the speed of tegmental hindbrain neurons using optogenetic tools and advanced track analysis optimized for in vivo migration. Finally, we introduce a compound screening assay to identify acetylcholine (ACh), glutamate, and glycine as regulators of migration, which act regionally along the neurons' route. We summarize our findings in a model describing how different neurotransmitters spatially interact to control neuronal migration. The high evolutionary conservation of the cerebellum and hindbrain makes it likely that polarization state-driven motility constitutes an important principle in building a functional brain.</description><identifier>ISSN: 1545-7885</identifier><identifier>ISSN: 1544-9173</identifier><identifier>EISSN: 1545-7885</identifier><identifier>DOI: 10.1371/journal.pbio.2002226</identifier><identifier>PMID: 29300740</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acetylcholine ; Biology and Life Sciences ; Brain ; Calcium ; Calcium (intracellular) ; Cell adhesion & migration ; Cell migration ; Cerebellum ; Circuits ; Cytomegalovirus ; Danio rerio ; Depolarization ; Embryogenesis ; Embryonic growth stage ; Embryos ; Evolutionary conservation ; Fourier transforms ; Funding ; Gene expression ; Glycine ; Hindbrain ; Hyperpolarization ; Medicine and Health Sciences ; Neurobiology ; Neurogenesis ; Neurons ; Neurosciences ; Neurotransmitters ; Physical Sciences ; Physiological aspects ; Proteins ; Regulators ; Research and Analysis Methods ; Software ; Studies ; Zebra fish ; Zebrafish</subject><ispartof>PLoS biology, 2018-01, Vol.16 (1), p.e2002226-e2002226</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Theisen U, Hennig C, Ring T, Schnabel R, Köster RW (2018) Neurotransmitter-mediated activity spatially controls neuronal migration in the zebrafish cerebellum. PLoS Biol 16(1): e2002226. https://doi.org/10.1371/journal.pbio.2002226</rights><rights>2018 Theisen et al 2018 Theisen et al</rights><rights>2018 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Theisen U, Hennig C, Ring T, Schnabel R, Köster RW (2018) Neurotransmitter-mediated activity spatially controls neuronal migration in the zebrafish cerebellum. 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Many neurons migrate in morphologically distinct stages that coincide with differentiation, requiring tight spatial regulation. It had been proposed that neurotransmitter-mediated activity could exert this control. Here, we demonstrate that intracellular calcium transients occur in cerebellar neurons of zebrafish embryos during migration. We show that depolarization increases and hyperpolarization reduces the speed of tegmental hindbrain neurons using optogenetic tools and advanced track analysis optimized for in vivo migration. Finally, we introduce a compound screening assay to identify acetylcholine (ACh), glutamate, and glycine as regulators of migration, which act regionally along the neurons' route. We summarize our findings in a model describing how different neurotransmitters spatially interact to control neuronal migration. The high evolutionary conservation of the cerebellum and hindbrain makes it likely that polarization state-driven motility constitutes an important principle in building a functional brain.</description><subject>Acetylcholine</subject><subject>Biology and Life Sciences</subject><subject>Brain</subject><subject>Calcium</subject><subject>Calcium (intracellular)</subject><subject>Cell adhesion & migration</subject><subject>Cell migration</subject><subject>Cerebellum</subject><subject>Circuits</subject><subject>Cytomegalovirus</subject><subject>Danio rerio</subject><subject>Depolarization</subject><subject>Embryogenesis</subject><subject>Embryonic growth stage</subject><subject>Embryos</subject><subject>Evolutionary conservation</subject><subject>Fourier transforms</subject><subject>Funding</subject><subject>Gene expression</subject><subject>Glycine</subject><subject>Hindbrain</subject><subject>Hyperpolarization</subject><subject>Medicine and Health 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Access Journals</collection><collection>PLoS Biology</collection><jtitle>PLoS biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Theisen, Ulrike</au><au>Hennig, Christian</au><au>Ring, Tobias</au><au>Schnabel, Ralf</au><au>Köster, Reinhard W</au><au>Stevens, Charles</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neurotransmitter-mediated activity spatially controls neuronal migration in the zebrafish cerebellum</atitle><jtitle>PLoS biology</jtitle><addtitle>PLoS Biol</addtitle><date>2018-01-04</date><risdate>2018</risdate><volume>16</volume><issue>1</issue><spage>e2002226</spage><epage>e2002226</epage><pages>e2002226-e2002226</pages><issn>1545-7885</issn><issn>1544-9173</issn><eissn>1545-7885</eissn><abstract>Neuronal migration during embryonic development contributes to functional brain circuitry. Many neurons migrate in morphologically distinct stages that coincide with differentiation, requiring tight spatial regulation. It had been proposed that neurotransmitter-mediated activity could exert this control. Here, we demonstrate that intracellular calcium transients occur in cerebellar neurons of zebrafish embryos during migration. We show that depolarization increases and hyperpolarization reduces the speed of tegmental hindbrain neurons using optogenetic tools and advanced track analysis optimized for in vivo migration. Finally, we introduce a compound screening assay to identify acetylcholine (ACh), glutamate, and glycine as regulators of migration, which act regionally along the neurons' route. We summarize our findings in a model describing how different neurotransmitters spatially interact to control neuronal migration. The high evolutionary conservation of the cerebellum and hindbrain makes it likely that polarization state-driven motility constitutes an important principle in building a functional brain.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29300740</pmid><doi>10.1371/journal.pbio.2002226</doi><orcidid>https://orcid.org/0000-0001-8395-5459</orcidid><oa>free_for_read</oa></addata></record> |
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| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central |
| subjects | Acetylcholine Biology and Life Sciences Brain Calcium Calcium (intracellular) Cell adhesion & migration Cell migration Cerebellum Circuits Cytomegalovirus Danio rerio Depolarization Embryogenesis Embryonic growth stage Embryos Evolutionary conservation Fourier transforms Funding Gene expression Glycine Hindbrain Hyperpolarization Medicine and Health Sciences Neurobiology Neurogenesis Neurons Neurosciences Neurotransmitters Physical Sciences Physiological aspects Proteins Regulators Research and Analysis Methods Software Studies Zebra fish Zebrafish |
| title | Neurotransmitter-mediated activity spatially controls neuronal migration in the zebrafish cerebellum |
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