Microglia: Dynamic Mediators of Synapse Development and Plasticity

Neuronal communication underlies all brain activity and the genesis of complex behavior. Emerging research has revealed an unexpected role for immune molecules in the development and plasticity of neuronal synapses. Moreover microglia, the resident immune cells of the brain, express and secrete immune-related signaling molecules that alter synaptic transmission and plasticity in the absence of inflammation. When inflammation does occur, microglia modify synaptic connections and synaptic plasticity required for learning and memory. Here we review recent findings demonstrating how the dynamic interactions between neurons and microglia shape the circuitry of the nervous system in the healthy brain and how altered neuron–microglia signaling could contribute to disease.

TrendsDuring brain development, complement-mediated engulfment of synapses by microglia is required for activity-dependent refinement of neuronal circuits.Microglia processes constantly move as they survey the surrounding environment. Increased neuronal activity triggers enhanced surveillance, which is characterized by ATP-mediated outgrowth of microglial processes.Microglia can modify activity-dependent changes in synaptic strength between neurons that underlie memory and learning using classical immunological signaling pathways involving cytokine release and NADPH oxidase activation.Altered immune system function in the brain triggered by inflammatory responses or immune dysregulation can lead to cognitive dysfunction and behavioral abnormalities.