A fundamental question in developmental neuroscience is how different cell types wire together with exquisite specificity to ensure the formation of canonical neural circuits. Increasingly, non-neural cells have been implicated as being essential to this process. Microglia-resident immune cells of the brain play crucial roles in refining synaptic connections. Favuzzi et al. show that GABA-receptive microglia interact with inhibitory synapses in developing mice 2 to 3 weeks after birth. Within this population of microglia, GABA promotes the selective pruning of inhibitory connectivity. Perturbing these specialized microglia caused long-lasting defects in inhibitory connectivity without affecting excitatory synapses and led to hyperactivity in adult animals. Thus, distinct microglial populations differentially engage with specific synapse types during development to modulate behavior.
Cell 184, P4048 (2021).