We showed that DAP12KI microglia cultured from P0 pups express higher levels of inflammatory markers such as NOS-2, IL1b, and IL6, as compared with their WT counterparts. The inflammatory status of DAP12KI was further confirmed by the EX 527 structure detection of a transient microgliosis in new-born, but not in adult mice brains. It has recently been demonstrated that in peripheral macrophages, DAP12 signaling is activator or inhibitor depending on the inflammatory context. It has been proposed that upon a BEZ235 abmole strong inflammatory stimulus such as a high level of LPS, DAP12 participates in activatory pathways, whereas at a low level of LPS, DAP12 may preferentially recruit inhibitory mediators. Our data suggest that in the developing brain, DAP12 is a downregulator of microglial activation. Neurons cultured from DAP12KI or inflamed P0 pups that were grown in a microglia-free and non-inflammatory environment display altered synaptic function. This demonstrates that prenatal inflammation suffices to alter synaptic function. However, this does not exclude the possibility that prenatal inflammation also has long-lasting effects on tissue and secondarily impacts neuronal or synaptic dysfunction. For instance, adult mice born to inflamed mother can display histological alterations or impaired neurogenesis, which may result in disturbance of neurotransmission. Similarly, old DAP12-deficient mice display hypomyelinosis in thalamus. Such deficiencies demonstrate persistent changes that we have not addressed in the present study. Together with white matter alteration, a synaptic degeneration has been described in the thalamus of DAP12-deficient mice, based on abnormal vesicles accumulations observed by electron microscopy. We did not detect morphological alterations of synapses in the hippocampus of DAP12KI by electron microscopy. Such a difference between the two studies may be due to differences in age, in the genetic background of the mice, or in the brain regions studied. Alternatively, the difference may arise from the fact that the vesicle accumulations, described as being a sign of synaptic degeneration, were not located in synapses as defined by the apposition of vesicles, presynaptic dense projections, synaptic cleft, and post-synaptic density. Rather, these accumulations may correspond to features that have been already described and are unrelated to synaptic dysfunction. Prenatal inflammation is known to differentially impact adult neuronal functions, depending on the inflammation-inducing protocol. In our study, we found that neurons cultured from maternally-inflamed pups display enhanced basal neuronal activity as compared with control. In contrast, basal activity was identical in neurons from DAP12KI and WT pups. This shows that the genetical and pharmacological inductions of prenatal microglial activation induce similar but not identical synaptic phenotypes. Such a difference may be due to TNFa, whose mRNA is not upregulated in DAP12KI microglia, but which is a hallmark of inflammation.