Microglia shape presynaptic properties at developing glutamatergic synapses

• DOI: 10.1002/glia.23508
• Publication Date: 2018-11-12T06:10:02Z
• Authors: Bernadette Basilico; Francesca Pagani; Alfonso Grimaldi; Barbara Cortese; Silvia Di Angelan...; Laetitia Weinhard; Cornelius Gross; Cristina Limatola; Laura Maggi; Davide Ragozzino
• Keywords: Mice, Knockout; Neurons; 0303 health sciences; CX3CR1; hippocampus; microglia; neuron-microglia interaction; synaptic development; synaptic transmission; hippocampus; Presynaptic Terminals; microglia; Excitatory Postsynaptic Potentials; Glutamic Acid; synaptic development; Hippocampus; Mice, Inbred C57BL; CX3CR1; Mice; 03 medical and health sciences; neuron-microglia interaction; Organ Culture Techniques; Synapses; synaptic transmission; Animals; Microglia

Deficient neuron-microglia signaling during brain development is associated with abnormal synaptic maturation. However, the precise impact of deficient microglia function on maturation and mechanisms involved remain poorly defined. Here we report that mice defective in neuron-to-microglia via fractalkine receptor (Cx3cr1 KO) show reduced microglial branching altered motility develop widespread deficits glutamatergic neurotransmission. We characterized functional properties CA3-CA1 synapses hippocampal slices from these found they display release probability, maintaining immature also at late developmental stages. In particular, CA1 Cx3cr1 KO (i) AMPA/NMDA ratio across time, displaying a normal NMDA component AMPA EPSC; (ii) connectivity, as demonstrated by current amplitudes input/output curve; (iii) greater facilitation paired pulse (PPR), suggesting decreased probability. addition, minimal stimulation experiments revealed excitatory have potency, but an increased number failures, confirming deficit presynaptic release. Consistently, were higher silent comparison to WT. The corrected performing conditions high probability (Ca2+ /Mg2+ 8), where showed multiplicity, ratio, proportion synapses. These results establish interactions profoundly influence function.