Structured and Target-Specific Development of Cortico-Cortical Connectivity in the Mouse Visual Cortex.

Area of Science:

• Neuroscience
• Developmental Biology
• Systems Neuroscience

Background:

• Mammalian cortex connectivity is stereotyped, but developmental principles for precise projection patterns are unclear.
• Two models exist: early exuberant outgrowth with pruning, or initially directed axonal targeting.

Purpose of the Study:

• To systematically map the postnatal development of V1 cortico-cortical projection neurons (CCPNs) to higher visual areas (HVAs) in mice.
• To resolve whether target specificity arises from pruning or directed targeting.

Main Methods:

• Utilized rapid and complementary retrograde, anterograde, and single-cell tracing methods.
• Employed multiplexed retrograde tracing and MAPseq for single-cell profiling.

Main Results:

• V1→HVA connectivity develops via staggered axon extension and pruning, aligned with target position.
• Individual V1 CCPNs establish specific projection motifs early with limited variation.
• Bidirectional V1-HVA connectivity refines gradually, with like-to-like connections aligning over development.

Conclusions:

• V1→HVA connections form via directed axonal targeting, establishing motifs early.
• Medial targets are innervated earlier and refine gradually; lateral targets are innervated later and refine rapidly.
• Feedforward and feedback V1-HVA circuits emerge concurrently and refine across development.