Microglia regulate chandelier cell axo-axonic synaptogenesis.
Nicholas B GalloArtan BerishaLinda Van AelstPublished in: Proceedings of the National Academy of Sciences of the United States of America (2022)
SignificanceChandelier cells (ChCs) are a unique type of GABAergic interneuron that form axo-axonic synapses exclusively on the axon initial segment (AIS) of neocortical pyramidal neurons (PyNs), allowing them to exert powerful yet precise control over PyN firing and population output. The importance of proper ChC function is further underscored by the association of ChC connectivity defects with various neurological conditions. Despite this, the cellular mechanisms governing ChC axo-axonic synapse formation remain poorly understood. Here, we identify microglia as key regulators of ChC axonal morphogenesis and AIS synaptogenesis, and show that disease-induced aberrant microglial activation perturbs proper ChC synaptic development/connectivity in the neocortex. In doing so, such findings highlight the therapeutic potential of manipulating microglia to ensure proper brain wiring.
Keyphrases
- inflammatory response
- resting state
- neuropathic pain
- white matter
- functional connectivity
- induced apoptosis
- spinal cord
- spinal cord injury
- lipopolysaccharide induced
- lps induced
- single cell
- cell cycle arrest
- transcription factor
- high glucose
- diabetic rats
- stem cells
- oxidative stress
- multiple sclerosis
- optic nerve
- mesenchymal stem cells
- signaling pathway
- endoplasmic reticulum stress
- cell proliferation