Microglial WNT5A supports dendritic spines maturation and neuronal firing

There is increasing evidence showing that microglia play a critical role in mediating synapse formation and spine growth, although the molecular mechanism remains elusive. Here, we demonstrate that the secreted morphogen WNT family member 5A (WNT5A) is the most abundant WNT expressed in microglia and that it promotes neuronal maturation. Co-culture of microglia with Thy1-YFP+ differentiated neurons significantly increased neuronal spine density and reduced dendritic spine turnover rate, which was diminished by silencing microglial Wnt5a in vitro. Co-cultured microglia increased post-synaptic marker PSD95 and synaptic density as determined by the co-localization of PSD95 with pre-synaptic marker VGLUT2 in vitro. The silencing of Wnt5a expression in microglia partially reduced both PSD95 and synaptic densities. Co-culture of differentiated neurons with microglia significantly enhanced neuronal firing rate as measured by multiple electrode array, which was significantly reduced by silencing microglial Wnt5a at 23 days differentiation in vitro. These findings demonstrate that microglia can mediate spine maturation and regulate neuronal excitability via WNT5A secretion indicating possible pathological roles of dysfunctional microglia in developmental disorders.

Automated summary

There is increasing evidence suggesting that microglia play a crucial role in synapse formation and spine growth, with the secreted morphogen WNT5A being the most abundant WNT expressed in microglia, promoting neuronal maturation. Co-culture of microglia with differentiated neurons showed increased neuronal spine density and reduced dendritic spine turnover rate, which decreased when microglial Wnt5a was silenced in vitro. Co-culture also increased post-synaptic marker PSD95 and synaptic density, while silencing Wnt5a in microglia reduced both. Furthermore, co-culture enhanced neuronal firing rate, which was reduced by silencing microglial Wnt5a during differentiation. These findings suggest the potential pathological roles of dysfunctional microglia in developmental disorders.