Astrocytes refine cortical connectivity at dendritic spines.

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

Astrocytes refine cortical connectivity at dendritic spines.

dc.contributor.author	Risher, WC
dc.contributor.author	Patel, S
dc.contributor.author	Kim, IH
dc.contributor.author	Uezu, A
dc.contributor.author	Bhagat, S
dc.contributor.author	Wilton, DK
dc.contributor.author	Pilaz, L
dc.contributor.author	Singh Alvarado, J
dc.contributor.author	Calhan, OY
dc.contributor.author	Silver, DL
dc.contributor.author	Stevens, B
dc.contributor.author	Calakos, N
dc.contributor.author	Soderling, SH
dc.contributor.author	Eroglu, C
dc.contributor.editor	Luo, L
dc.coverage.spatial	England
dc.date.accessioned	2015-01-15T19:23:13Z
dc.date.issued	2014-12-17
dc.description.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.
dc.identifier	http://www.ncbi.nlm.nih.gov/pubmed/25517933
dc.identifier.eissn	2050-084X
dc.identifier.uri	https://hdl.handle.net/10161/9362
dc.language	eng
dc.publisher	eLife Sciences Publications, Ltd
dc.relation.ispartof	Elife
dc.relation.isversionof	10.7554/eLife.04047
dc.subject	astrocytes
dc.subject	cell biology
dc.subject	dendritic spines
dc.subject	mouse
dc.subject	neuroscience
dc.subject	synaptogenesis
dc.subject	thalamocortical
dc.subject	Animals
dc.subject	Astrocytes
dc.subject	Calcium-Binding Proteins
dc.subject	Dendritic Spines
dc.subject	Extracellular Matrix Proteins
dc.subject	Mice
dc.subject	Microscopy, Confocal
dc.subject	Microscopy, Immunoelectron
dc.subject	Synapses
dc.title	Astrocytes refine cortical connectivity at dendritic spines.
dc.type	Journal article
duke.contributor.orcid	Silver, DL\|0000-0001-9189-844X
duke.contributor.orcid	Eroglu, C\|0000-0002-7204-0218
pubs.author-url	http://www.ncbi.nlm.nih.gov/pubmed/25517933
pubs.organisational-group	Basic Science Departments
pubs.organisational-group	Cell Biology
pubs.organisational-group	Clinical Science Departments
pubs.organisational-group	Duke
pubs.organisational-group	Duke Cancer Institute
pubs.organisational-group	Duke Institute for Brain Sciences
pubs.organisational-group	Institutes and Centers
pubs.organisational-group	Institutes and Provost's Academic Units
pubs.organisational-group	Molecular Genetics and Microbiology
pubs.organisational-group	Neurobiology
pubs.organisational-group	Neurology
pubs.organisational-group	Neurology, Movement Disorders
pubs.organisational-group	School of Medicine
pubs.organisational-group	Staff
pubs.organisational-group	University Institutes and Centers
pubs.publication-status	Published online
pubs.volume	3

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