Astrocyte-dependent circuit remodeling by synapse phagocytosis

In the central nervous system, synaptic pruning, the removal of unnecessary synaptic contacts, is an essential process for proper circuit maturation in neurodevelopment as well as for synaptic homeostasis in the adult stage. Dysregulation of synaptic pruning can contribute to the initiation and progres-sion of various mental disorders, such as schizophrenia and depression, as well as neurodegenerative diseases including Alzheimer's disease. In the past 15 years, pioneering works have demonstrated that different types of glial cells regulate the number of synapses by selectively eliminating them through phagocytic molecular machinery. Although a majority of findings have been focused on microglia, it is increasingly evident that astrocytes function as a critical player in activity -dependent synapse elimination in developing, adult, and diseased brains. In this review, we will discuss recent findings showing the mechanisms and physiological importance of astrocyte-mediated synapse elimination in controlling synap-ses and circuit homeostasis. We propose that astrocytes play dominant and non-redundant roles in eliminating synapses during the activity-dependent circuit remodeling processes that do not involve neuro-inflammation.

Automated summary

In the central nervous system, synaptic pruning is crucial for circuit maturation in neurodevelopment and synaptic homeostasis. Dysregulation of synaptic pruning is implicated in various mental disorders and neurodegenerative diseases. Recent studies have shown that glial cells, particularly microglia and astrocytes, play important roles in eliminating synapses through phagocytic mechanisms. This review discusses the mechanisms and physiological significance of astrocyte-mediated synapse elimination and proposes their dominant role in activity-dependent circuit remodeling.