MICROGLIA-NEURON INTERACTIONS IN NEOCORTICAL LAYER 1

Microglia are the primary immune cells of the central nervous system. Yet, microglial remodeling of neural circuit connectivity in development and adulthood, and microglial dysfunctions in some brain disorders pathogenesis indicate important non-immune functions. Nevertheless, a causal involvement of microglia in modulating neural activity, learning and memory functions in physiological conditions remains unclear. Here we addressed this question, focusing on microglia interactions with neocortical layer 1 NDNF inhibitory interneurons. Layer 1 neuroimmune interactions are particularly interesting given its integration of top-down and bottom-up information, inhibitory control of downstream circuit and proximity with the meninges. To address these questions, we employed transient, whole-brain pharmacological depletion of microglia in adult mice together with in vitro electrophysiological recordings, in vivo two-photon calcium imaging and auditory threat conditioning. Furthermore, we performed preliminary investigations of the impact of TNFa immune pathway on neuronal activity in vitro. Our current data suggest that microglia depletion robustly affects the memory formed in a layer 1-dependent auditory threat learning paradigm. Moreover, subsequent threat memory extinction was enhanced in microglia-depleted animals. These observations suggest a role for microglia in neocortical memory in the adult healthy brain, and motivate further research on the underlying mechanisms.