Astrocytes refine cortical connectivity at dendritic spines.
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 articleSubject
astrocytescell biology
dendritic spines
mouse
neuroscience
synaptogenesis
thalamocortical
Animals
Astrocytes
Calcium-Binding Proteins
Dendritic Spines
Extracellular Matrix Proteins
Mice
Microscopy, Confocal
Microscopy, Immunoelectron
Synapses
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https://hdl.handle.net/10161/9362Published Version (Please cite this version)
10.7554/eLife.04047Publication 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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Show full item recordScholars@Duke
Nicole Calakos
Lincoln Financial Group Distinguished Professor of Neurobiology
Cagla Eroglu
Associate Professor of Cell Biology
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
Scott Haydn Soderling
George Barth Geller Distinguished Professor of Molecular Biology
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