title: Axon initial segment-associated microglia.
abstract: Microglia are the brain's resident immune cells and function as the main defense against pathogens or injury. However, in the absence of disease, microglia have other functions in the normal brain. For example, previous studies showed that microglia contribute to circuit refinement and synaptic plasticity in the developing and adult brain, respectively. Thus, microglia actively participate in regulating neuronal excitability and function. Here, we report that in the cortex, but not other brain regions, a subset of microglia extend a single process that specifically associates and overlaps with the axon initial segment (AIS), the site where action potentials are generated. Similar associations were not observed with dendrites or distal axons. Microglia-AIS interactions appear early in development, persist throughout adulthood, and are conserved across species including mice, rats, and primates. However, these interactions are lost after microglial activation following brain injury, suggesting that such interactions may be part of healthy brain function. Loss of microglial CX3CR1 receptors, or the specialized extracellular matrix surrounding the AIS, did not disrupt the interaction. However, loss of AIS proteins by the neuron-specific deletion of the master AIS scaffold AnkyrinG disrupted microglia-AIS interactions. These results reveal a unique population of microglia that specifically interact with the AIS in the adult cortex.
authors: Department of Neuroscience.
authors: Kelli
authors: K
authors: Baalman
authors: Department of Neuroscience.
authors: Miguel A
authors: MA
authors: Marin
authors: Program in Developmental Biology, and.
authors: Tammy Szu-Yu
authors: TS
authors: Ho
authors: Department of Neuroscience.
authors: Marlesa
authors: M
authors: Godoy
authors: Department of Neurosurgery, Baylor College of Medicine, Houston, Texas 77030.
authors: Leela
authors: L
authors: Cherian
authors: Department of Neuroscience, Department of Neurosurgery, Baylor College of Medicine, Houston, Texas 77030.
authors: Claudia
authors: C
authors: Robertson
authors: Department of Neuroscience, Program in Developmental Biology, and Rasband@bcm.edu.
authors: Matthew N
authors: MN
authors: Rasband
mesh_terms: D000200:Action Potentials; D000818:Animals; D017487:Ankyrins / Q000235:genetics / Q000378:metabolism; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D001930:Brain Injuries / Q000473:pathology; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D003712:Dendrites / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019707:Receptors, Chemokine / Q000378:metabolism
chemical_list: D017487:Ankyrins; D019707:Receptors, Chemokine
keywords: axon; axon initial segment; brain injury; glia; ion channel; microglia
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