Astrocytes refine cortical connectivity at dendritic spines.

Area of Science:

• Neuroscience
• Developmental Biology
• Cell Biology

Background:

• Thalamocortical (TC) axons must form connections in the cortex amidst numerous intracortical projections.
• The mechanisms governing TC synapse formation and maintenance in this competitive environment are not fully understood.

Purpose of the Study:

• To investigate the role of astrocyte-secreted protein hevin in establishing thalamocortical synaptic connectivity during cortical development.
• To elucidate how hevin influences the formation and refinement of excitatory synapses at dendritic spines.

Main Methods:

• Utilized mouse models with hevin deficiency.
• Employed serial section electron microscopy (ssEM) for 3D reconstruction of cortical neurons.
• Conducted immunoelectron microscopy (Immuno-EM) and confocal microscopy analyses.

Main Results:

• Absence of hevin led to a significant and persistent reduction in thalamocortical synapses.
• Hevin deficiency caused a temporary increase in intracortical excitatory connections.
• Spines with multiple excitatory contacts (SMECs), normally decreasing with development, remained abundant in hevin-null mice, indicating impaired synaptic refinement.

Conclusions:

• Astrocyte-secreted hevin is essential for normal thalamocortical synapse development and maintenance.
• Hevin plays a critical role in regulating synaptic refinement at dendritic spines by controlling the proportion of spines receiving multiple inputs.
• Astrocytes actively modulate synaptic connectivity through secreted factors like hevin, influencing neural circuit formation.