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Active zone compaction correlates with presynaptic homeostatic potentiation.

Achmed Mrestani1, Martin Pauli2, Philip Kollmannsberger3

  • 1Institute for Physiology, Department of Neurophysiology, Julius Maximilians University Würzburg, 97070 Würzburg, Germany; Department of Neurology, Leipzig University Medical Center, 04103 Leipzig, Germany.

Cell Reports
|October 5, 2021
PubMed
Summary

Presynaptic homeostatic potentiation (PHP) compacts active zones (AZs) by reorganizing scaffold proteins, not by increasing their numbers. This AZ compaction explains apparent increases in size during homeostatic plasticity.

Keywords:
BruchpilotRIM-binding proteinactive zonecompactionhomeostasispresynaptic plasticitysuper-resolution microscopy

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Synaptic Plasticity

Background:

  • Homeostatic plasticity stabilizes neurotransmitter release.
  • Presynaptic homeostatic potentiation (PHP) involves active zone (AZ) reorganization.
  • Previous studies suggested AZ enlargement in PHP.

Purpose of the Study:

  • Investigate AZ plasticity during PHP at the synaptic mesoscale.
  • Clarify the role of scaffold protein quantity and organization in PHP.

Main Methods:

  • Direct stochastic optical reconstruction microscopy (dSTORM) for high-resolution imaging.
  • Hierarchical density-based spatial clustering of applications with noise (HDBSCAN) for AZ analysis.
  • Correlative confocal and dSTORM imaging.

Main Results:

  • PHP induces compaction of individual AZs.
  • Scaffold protein (Bruchpilot, RIM-binding protein) copy numbers remain unchanged.
  • AZ compaction, including subcluster movement, occurs in both acute and chronic PHP.
  • AZ compaction explains apparent increases in AZ area and protein content.

Conclusions:

  • PHP reorganizes AZ structure through compaction, not addition of proteins.
  • AZ compaction is a key mechanism underlying presynaptic homeostatic plasticity.