Sonic hedgehog signaling in astrocytes mediates cell type-specific synaptic organization
Astrocytes have emerged as integral partners with neurons in regulating synapse formation and function, but the mechanisms that mediate these interactions are not well understood. Here, we show that Sonic hedgehog (Shh) signaling in mature astrocytes is required for establishing structural organizat...
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doaj-11e26469fdde4824846a42dedc8da8f82021-05-05T17:41:16ZengeLife Sciences Publications LtdeLife2050-084X2019-06-01810.7554/eLife.45545Sonic hedgehog signaling in astrocytes mediates cell type-specific synaptic organizationSteven A Hill0Andrew S Blaeser1Austin A Coley2Yajun Xie3Katherine A Shepard4Corey C Harwell5Wen-Jun Gao6A Denise R Garcia7https://orcid.org/0000-0001-5809-3543Department of Biology, Drexel University, Philadelphia, United StatesDepartment of Biology, Drexel University, Philadelphia, United StatesDepartment of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Biology, Drexel University, Philadelphia, United StatesDepartment of Neurobiology, Harvard Medical School, Boston, United StatesDepartment of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, United StatesDepartment of Biology, Drexel University, Philadelphia, United States; Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, United StatesAstrocytes have emerged as integral partners with neurons in regulating synapse formation and function, but the mechanisms that mediate these interactions are not well understood. Here, we show that Sonic hedgehog (Shh) signaling in mature astrocytes is required for establishing structural organization and remodeling of cortical synapses in a cell type-specific manner. In the postnatal cortex, Shh signaling is active in a subpopulation of mature astrocytes localized primarily in deep cortical layers. Selective disruption of Shh signaling in astrocytes produces a dramatic increase in synapse number specifically on layer V apical dendrites that emerges during adolescence and persists into adulthood. Dynamic turnover of dendritic spines is impaired in mutant mice and is accompanied by an increase in neuronal excitability and a reduction of the glial-specific, inward-rectifying K+ channel Kir4.1. These data identify a critical role for Shh signaling in astrocyte-mediated modulation of neuronal activity required for sculpting synapses.https://elifesciences.org/articles/45545astrocytesynapseSonic hedgehogplasticitydevelopmentspines |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Steven A Hill Andrew S Blaeser Austin A Coley Yajun Xie Katherine A Shepard Corey C Harwell Wen-Jun Gao A Denise R Garcia |
spellingShingle |
Steven A Hill Andrew S Blaeser Austin A Coley Yajun Xie Katherine A Shepard Corey C Harwell Wen-Jun Gao A Denise R Garcia Sonic hedgehog signaling in astrocytes mediates cell type-specific synaptic organization eLife astrocyte synapse Sonic hedgehog plasticity development spines |
author_facet |
Steven A Hill Andrew S Blaeser Austin A Coley Yajun Xie Katherine A Shepard Corey C Harwell Wen-Jun Gao A Denise R Garcia |
author_sort |
Steven A Hill |
title |
Sonic hedgehog signaling in astrocytes mediates cell type-specific synaptic organization |
title_short |
Sonic hedgehog signaling in astrocytes mediates cell type-specific synaptic organization |
title_full |
Sonic hedgehog signaling in astrocytes mediates cell type-specific synaptic organization |
title_fullStr |
Sonic hedgehog signaling in astrocytes mediates cell type-specific synaptic organization |
title_full_unstemmed |
Sonic hedgehog signaling in astrocytes mediates cell type-specific synaptic organization |
title_sort |
sonic hedgehog signaling in astrocytes mediates cell type-specific synaptic organization |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2019-06-01 |
description |
Astrocytes have emerged as integral partners with neurons in regulating synapse formation and function, but the mechanisms that mediate these interactions are not well understood. Here, we show that Sonic hedgehog (Shh) signaling in mature astrocytes is required for establishing structural organization and remodeling of cortical synapses in a cell type-specific manner. In the postnatal cortex, Shh signaling is active in a subpopulation of mature astrocytes localized primarily in deep cortical layers. Selective disruption of Shh signaling in astrocytes produces a dramatic increase in synapse number specifically on layer V apical dendrites that emerges during adolescence and persists into adulthood. Dynamic turnover of dendritic spines is impaired in mutant mice and is accompanied by an increase in neuronal excitability and a reduction of the glial-specific, inward-rectifying K+ channel Kir4.1. These data identify a critical role for Shh signaling in astrocyte-mediated modulation of neuronal activity required for sculpting synapses. |
topic |
astrocyte synapse Sonic hedgehog plasticity development spines |
url |
https://elifesciences.org/articles/45545 |
work_keys_str_mv |
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