A microglia-cytokine axis to modulate synaptic connectivity and function

[Display omitted] •Microglial cytokine signaling regulates axon outgrowth and synaptogenesis.•CX3CR1 regulates microglial recruitment to synapses necessary for synaptic maturation.•Microglial CX3CR1, TNFα, and IL-1β modulate synaptic transmission and plasticity.•Microglial cytokine signaling at synapses has important implications for disease. Microglia have recently been recognized as key regulators of synapse development, function, and plasticity. Critical to progressing the field is the identification of molecular underpinnings necessary for microglia to carry out these important functions within neural circuits. Here, we focus a review specifically on roles for microglial cytokine signaling within developing and mature neural circuits. We review exciting new studies demonstrating essential roles for microglial cytokine signaling in axon outgrowth, synaptogenesis and synapse maturation during development, as well as synaptic transmission and plasticity in adulthood. Together, these studies identify microglia and cytokines as critical modulators of neural circuits within the healthy brain, with implications for a broad range of neurological disorders with disruptions in synaptic structure and function.