ALTERED MICROGLIA-PVI INTERACTIONS IN DISC1 MUTANT MICE

Microglia, the resident immune cells of the brain, are involved in virtually all CNS disorders, with implications ranging from neuroprotection to neurodegeneration, depending on the activation state and the resulting impact on neuronal function. While their interactions with excitatory neurons are relatively well-explored, there is only sparse knowledge on how microglia regulate GABAergic inhibition, for which parvalbumin positive interneurons (PVI) play a crucial role. PVIs are a key component in coordinating neuronal activity underlying memory formation, cognition and sensory information processing, but are also implicated in neuropsychiatric disorders. Here, we investigate microglia-PVI bidirectional interactions in the hippocampus of an adult Disrupted in-Schizophrenia 1 (DISC1) mouse model, characterized by impairment of PVI-dependent network function reflected in aberrant gamma oscillatory network activity. To address this, we combined in vivo local field potential recordings, alongside confocal and multiphoton imaging techniques. We observed that microglia in DISC1 mutant mice exhibit altered morphology, lysosomal function and phagocytosis, as well as closer interactions with PVI perisomatic regions. Moreover, we identified changes in perineuronal nets (PNNs) along with larger amounts of incorporated PNN material in microglia in DISC1 mice. Our findings suggest that microglial activation in DISC1 mice contributes to the changes in local network activity by affecting PVI function.