Astrocytes refine cortical connectivity at dendritic spines.
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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.
Extracellular Matrix Proteins
Published Version (Please cite this version)10.7554/eLife.04047
Publication InfoBhagat, S; Calakos, Nicole; Calhan, OY; Eroglu, C; Kim, IH; Patel, S; ... Wilton, DK (2014). Astrocytes refine cortical connectivity at dendritic spines. Elife, 3. 10.7554/eLife.04047. Retrieved from http://hdl.handle.net/10161/9362.
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Professor in Neurology
Associate Professor of Cell Biology
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
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