Glial responses to synaptic damage and plasticity.

We review three principally different forms of injury-induced synaptic alterations. (1) Displacement of presynaptic terminals from perikarya and dendrites of axotomized neurons, (2) central changes in primary afferent terminals of peripherally axotomized sensory ganglion cells, and (3) anterograde Wallerian-type degeneration following interruption of central axonal pathways. All these instances rapidly activate astrocytes and microglia in the vicinity of the affected synaptic terminals. The evidence suggests that activated astrocytes play important and direct roles in synapse elimination and in the processes mediating collateral reinnervation. The roles of microglia are enigmatic. They undergo activation close to axotomized motoneuron perikarya, where synapse displacement occurs, but not adjacent to axotomized intrinsic central nervous system neurons, where synapse displacement also occurs. Microglia are also rapidly activated around central primary sensory terminals of peripherally axotomized sensory ganglion cells. Occasional phagocytosis of degenerating axon terminals by microglia occur in the latter situation. However, the role of microglia may be more oriented toward the general tissue conditions rather than specifically toward synaptic terminals.