Combinatorial expression of γ-protocadherins regulates synaptic connectivity in the mouse neocortex

Area of Science:

• Neuroscience
• Molecular Biology
• Developmental Biology

Background:

• Neuronal connectivity requires precise partner selection and avoidance of inappropriate connections.
• Mechanisms preventing unwanted synaptic associations are largely unexplored.

Purpose of the Study:

• To investigate the role of clustered protocadherin gamma (γ-PCDH) in orchestrating synaptic connectivity.
• To elucidate the molecular strategies neurons use to avoid undesirable connections.

Main Methods:

• Single-cell 5' end sequencing to analyze γ-PCDH combinatorial expression patterns.
• Whole-cell patch-clamp recordings to assess synaptic connectivity.

Main Results:

• Identified intricate combinatorial expression patterns of γ-PCDH variable isoforms in neocortical neurons.
• Demonstrated an inverse correlation between the similarity of γ-PCDH combinatorial patterns and synaptic connectivity.

Conclusions:

• Combinatorial γ-PCDH expression is a key regulator of synaptic connectivity in the mouse neocortex.
• This mechanism provides a sophisticated molecular strategy for constructing specific neural networks and avoiding aberrant connections.