Figure 2.

The role of microglia in developmental, activity-dependent synaptic remodeling. (A) A model in which microglia selectively engulf a subset of less active, intact synapses. Data suggest that a signal (e.g., fractalkine) recruits microglia to remodeling synapses. Those synapses that are less active (light gray) are molecularly “tagged” with “eat-me” signals (e.g., complement). Microglia, expressing receptors for “eat-me” signals (e.g., CR3), actively select and phagocytose intact synaptic components. (B) A model whereby neurons autonomously begin to prune (retract and/or fragment) before engulfment by microglia. Data suggest that a recruitment signal (e.g., fractalkine) recruits microglia to remodeling synapses. Those synapses that are less active (light gray) begin to autonomously retract and/or fragment. These pruning synapses are subsequently “tagged” with “eat-me” signals (e.g., complement), followed by engulfment by microglia, which express receptors for “eat-me” signals (e.g., CR3).