Microglia-neuron crosstalk: Signaling mechanism and control of synaptic transmission

The continuous crosstalk between microglia and neurons is required for microglia housekeeping functions and contributes to brain homeostasis. Through these exchanges, microglia take part in crucial brain functions, including development and plasticity. The alteration of neuron-microglia communication contributes to brain disease states with consequences, ranging from synaptic function to neuronal survival. This review focuses on the signaling pathways responsible for neuron-microglia crosstalk, highlighting their physiological roles and their alteration or specific involvement in disease. In particular, we discuss studies, establishing how these signaling allow microglial cells to control relevant physiological functions during brain development, including synaptic formation and circuit refinement. In addition, we highlight how microglia and neurons interact functionally to regulate highly dynamical synaptic functions. Microglia are able to release several signaling molecules involved in the regulation of synaptic activity and plasticity. On the other side, molecules of neuronal origin control microglial processes motility in an activity-dependent manner. Indeed, the continuous crosstalk between microglia and neurons is required for the sensing and housekeeping functions of microglia and contributes to the maintenance of brain homeostasis and, particularly, to the sculpting of neuronal connections during development. These interactions lay on the delicate edge between physiological processes and homeostasis alteration in pathology and are themselves altered during neuroinflammation. The full description of these processes could be fundamental for understanding brain functioning in health and disease.