Correlative Assembly of Subsynaptic Nanoscale Organizations During Development

Area of Science:

• Neuroscience
• Cell Biology
• Developmental Biology

Background:

• Nanoscale organization of synaptic proteins is crucial for efficient neurotransmitter release and synaptic transmission.
• The developmental mechanisms underlying the formation of these nano-architectures remain largely unknown.

Purpose of the Study:

• To investigate the developmental changes in subsynaptic protein organization during synapse maturation.
• To determine the role of synaptic activity in the formation of trans-synaptic nanocolumns.

Main Methods:

• Utilized super-resolution stochastic optical reconstruction microscopy (STORM) imaging.
• Analyzed the organization of RIM1/2, GluA1, and PSD-95 during synapse maturation in cultured hippocampal neurons.
• Examined the effects of inhibiting action potentials or AMPA receptors on synaptic organization.

Main Results:

• Synaptic cluster volume and subsynaptic heterogeneity increased with synapse maturation.
• Presynaptic and postsynaptic compartment sizes correlated across all stages.
• Mature synapses showed correlated presynaptic and postsynaptic nano-organizations.
• Inhibiting synaptic activity increased cluster volume and heterogeneity but preserved trans-synaptic alignment.

Conclusions:

• Synaptic nanocolumns are organized through an intrinsic mechanism.
• Nanocolumn formation is independent of synaptic activity and action potentials.
• These findings elucidate the developmental process of subsynaptic protein architecture.