Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 42, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2106294118j1of10
Keywords
microglia; phagocytosis; synaptic pruning
Categories
Funding
- European Research Council
- Wellcome Investigator Awards [099222]
- Wellcome Trust
- Chulabhorn Royal Academy PhD studentship
Ask authors/readers for more resources
Microglia are immune cells in the central nervous system responsible for phagocytosing redundant synapses and debris. The THIK-1 K+ channels play a crucial role in regulating microglial phagocytosis and synaptic pruning. Changes in THIK-1 expression levels may impact neural circuit function.
Microglia are the resident immune cells of the central nervous system. They constantly survey the brain parenchyma for redundant synapses, debris, or dying cells, which they remove through phagocytosis. Microglial ramification, motility, and cytokine release are regulated by tonically active THIK-1 K+ channels on the microglial plasma membrane. Here, we examined whether these channels also play a role in phagocytosis. Using pharmacological blockers and THIK-1 knockout (KO) mice, we found that a lack of THIK-1 activity approximately halved both microglial phagocytosis and marker levels for the lysosomes that degrade phagocytically removed material. These changes may reflect a decrease of intracellular [Ca2+]i activity, which was observed when THIK-1 activity was reduced, since buffering [Ca2+]i reduced phagocytosis. Less phagocytosis is expected to result in impaired pruning of synapses. In the hippocampus, mice lacking THIK-1 expression had an increased number of anatomically and electrophysiologically defined glutamatergic synapses during development. This resulted from an increased number of presynaptic terminals, caused by impaired removal by THIK-1 KO microglia. The dependence of synapse number on THIK-1 K+ channels, which control microglial surveillance and phagocytic ability, implies that changes in the THIK-1 expression level in disease states may contribute to altering neural circuit function.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available