Glia orchestrate neural circuit development

Over the past ∼25 years, our understanding of neural circuit development in the central nervous system has shifted. Once considered passive supporters, glial cells, namely, astrocytes, oligodendrocyte lineage cells, and microglia, are increasingly recognized as active regulators of developmental circuit formation and maturation. In this review, we synthesize evidence for the multifaceted functions by which glial cells instruct neuronal circuit establishment and maturation across developmental stages and in both vertebrate and invertebrate nervous systems. We describe the programs deployed to guide successive phases of synapse formation, refinement, plasticity, and stabilization in a circuit- and experience-dependent manner. We also highlight how an extensive glia-glia communication repertoire provides another critical layer of control over development. In summary, glia cooperatively shape circuit development by instructing, stabilizing, or eliminating specific wiring programs. Disruption of this coordinated logic, beyond dysfunction of any single glial or neuronal process, underlies vulnerability to neurodevelopmental and neuropsychiatric disease.