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Microglia regulate chandelier cell axo-axonic synaptogenesis.

Nicholas B Gallo1,2, Artan Berisha1, Linda Van Aelst1

  • 1Division of Neuroscience, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724.

Proceedings of the National Academy of Sciences of the United States of America
|March 9, 2022
PubMed
Summary

Microglia regulate chandelier cell (ChC) development and synapse formation on pyramidal neurons. Aberrant microglial activation disrupts ChC connectivity, suggesting microglia as a therapeutic target for neurological disorders.

Keywords:
axon initial segmentchandelier cellsinflammationmicrogliasynaptogenesis

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Area of Science:

  • Neuroscience
  • Cellular Biology
  • Synaptic Plasticity

Background:

  • Chandelier cells (ChCs) are crucial GABAergic interneurons forming axo-axonic synapses on pyramidal neuron (PyN) axon initial segments (AIS).
  • Defects in ChC connectivity are linked to neurological conditions, yet the mechanisms of their synapse formation are poorly understood.

Purpose of the Study:

  • To investigate the cellular mechanisms governing ChC axo-axonic synapse formation.
  • To identify the role of microglia in ChC axonal development and synaptic connectivity.

Main Methods:

  • Utilized advanced microscopy techniques to observe ChC axonal morphogenesis.
  • Investigated microglial activation states and their impact on ChC synaptogenesis in vivo and in vitro.
  • Examined ChC-PyN connectivity in models of aberrant microglial activation.

Main Results:

  • Identified microglia as critical regulators of ChC axonal growth and AIS synaptogenesis.
  • Demonstrated that disease-induced microglial activation impairs ChC synaptic development and connectivity in the neocortex.
  • Showcased the direct impact of microglial state on the formation of precise neuronal circuits.

Conclusions:

  • Microglia play a pivotal role in the proper wiring of neocortical circuits by regulating ChC development.
  • Aberrant microglial activation poses a significant risk to ChC synaptic function and brain wiring.
  • Targeting microglia presents a potential therapeutic strategy for neurological disorders associated with ChC dysfunction.