Microglia Depletion Selectively Eliminates a Singular Form of Hippocampal Long-Term Potentiation

Abstract There has been considerable recent interest in the possibility that microglia contribute to synaptic plasticity and some forms of learning. We report here that elimination of the cells in young adult male mice with a 7-12 day treatment with an antagonist (PLX5622) of the colony stimulating factor 1 receptor causes a profound but highly selective impairment to long-term potentiation (LTP) expressed by lateral perforant path (LPP) synapses with the dentate gyrus. Input/output functions and frequency facilitation to repetitive stimulation were not measurably affected. Direct infusion of PLX5622 into slices from naiive mice did not reduce the magnitude of LPP-LTP. Microglial depletion had no detectable effect on LTP in either the medial perforant path input to the dentate gyrus or the Schaffer-commissural projections between fields CA3 and CA1. We conclude that microglia discretely regulate the unusual form of LTP expressed by the LPP and thus exert region-specific effects on circuit function within hippocampus.