Microglia-mediated synaptic pruning as a key deficit in neurodevelopmental disorders: Hype or hope?

There is a consensus in the field that microglia play a prominent role in neurodevelopmental processes like synaptic pruning and neuronal network maturation. Thus, a current momentum of associating microglia deficits with neurodevelopmental disorders (NDDs) emerged. This concept is challenged by rodent studies and clinical data. Intriguingly, reduced numbers of microglia or altered microglial functions do not necessarily lead to overt NDD phenotypes, and neuropsychiatric symptoms seem to develop primarily in adulthood. Hence, it remains open for discussion whether microglia are truly indispensable for healthy neurodevelopment. Here, we critically discuss the role of microglia in synaptic pruning and highlight area- and age dependency. We propose an updated model of microglia-mediated synaptic pruning in the context of NDDs and discuss the potential of targeting microglia for treatment of these disorders.