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Astrocytes refine cortical connectivity at dendritic spines.

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Date
2014-12-17
Authors
Risher, WC
Patel, S
Kim, IH
Uezu, A
Bhagat, S
Wilton, DK
Pilaz, L
Singh Alvarado, J
Calhan, OY
Silver, DL
Stevens, B
Calakos, N
Soderling, SH
Eroglu, C
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Abstract
During cortical synaptic development, thalamic axons must establish synaptic connections despite the presence of the more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is unknown. Here, we show that astrocyte-secreted protein hevin is required for normal thalamocortical synaptic connectivity in the mouse cortex. Absence of hevin results in a profound, long-lasting reduction in thalamocortical synapses accompanied by a transient increase in intracortical excitatory connections. Three-dimensional reconstructions of cortical neurons from serial section electron microscopy (ssEM) revealed that, during early postnatal development, dendritic spines often receive multiple excitatory inputs. Immuno-EM and confocal analyses revealed that majority of the spines with multiple excitatory contacts (SMECs) receive simultaneous thalamic and cortical inputs. Proportion of SMECs diminishes as the brain develops, but SMECs remain abundant in Hevin-null mice. These findings reveal that, through secretion of hevin, astrocytes control an important developmental synaptic refinement process at dendritic spines.
Type
Journal article
Subject
astrocytes
cell biology
dendritic spines
mouse
neuroscience
synaptogenesis
thalamocortical
Animals
Astrocytes
Calcium-Binding Proteins
Dendritic Spines
Extracellular Matrix Proteins
Mice
Microscopy, Confocal
Microscopy, Immunoelectron
Synapses
Permalink
https://hdl.handle.net/10161/9362
Published Version (Please cite this version)
10.7554/eLife.04047
Publication Info
Risher, WC; Patel, S; Kim, IH; Uezu, A; Bhagat, S; Wilton, DK; ... Eroglu, C (2014). Astrocytes refine cortical connectivity at dendritic spines. Elife, 3. 10.7554/eLife.04047. Retrieved from https://hdl.handle.net/10161/9362.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Calakos

Nicole Calakos

Lincoln Financial Group Distinguished Professor of Neurobiology
Eroglu

Cagla Eroglu

Associate Professor of Cell Biology
Silver

Debra Lynn Silver

Associate Professor of Molecular Genetics and Microbiology
How is the brain assembled and sculpted during embryonic development?  Addressing this question has enormous implications for understanding neurodevelopmental disorders affecting brain size and function. In evolutionary terms, our newest brain structure is the cerebral cortex, which drives higher cognitive capacities. The overall mission of my research lab is to elucidate genetic and cellular mechanisms controlling cortical development and contributing to neurodevelopmental patho
Soderling

Scott Haydn Soderling

George Barth Geller Distinguished Professor of Molecular Biology
Alphabetical list of authors with Scholars@Duke profiles.
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