Astrocytes refine cortical connectivity at dendritic spines.

Elife
Publication type
Journal Article
Authors
Keywords
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.

Year of Publication
2014
Journal
Elife
Volume
3
Date Published
2014 Dec 17
ISSN
2050-084X
DOI
10.7554/eLife.04047
PubMed ID
25517933
PubMed Central ID
PMC4286724
Links
Grant list
NS059957 / NS / NINDS NIH HHS / United States
1F32NS083283 / NS / NINDS NIH HHS / United States
R01 NS059957 / NS / NINDS NIH HHS / United States
T32 GM007184 / GM / NIGMS NIH HHS / United States
R56 NS059957 / NS / NINDS NIH HHS / United States
NS071008 / NS / NINDS NIH HHS / United States
R01 NS083897 / NS / NINDS NIH HHS / United States
P30 HD018655 / HD / NICHD NIH HHS / United States
MH103374 / MH / NIMH NIH HHS / United States
NS083897 / NS / NINDS NIH HHS / United States
F32 NS083283 / NS / NINDS NIH HHS / United States
T32 NS051156 / NS / NINDS NIH HHS / United States
R01 DA031833 / DA / NIDA NIH HHS / United States
R01 MH103374 / MH / NIMH NIH HHS / United States
2T32NS51156-6 / NS / NINDS NIH HHS / United States
T32 GM007171 / GM / NIGMS NIH HHS / United States
R01 NS071008 / NS / NINDS NIH HHS / United States