Fig. 1.

Schematic depiction of the current state of the literature. Upon being challenged with a bacterial or viral infection, a surgery, or a head injury, once quiescent microglia of the young adult animal are rapidly and transiently activated. Pro-inflammatory cytokines are released resulting in only modest elevations above basal levels, and lasting no longer than 24 h. Synaptic facilitation (LTP) and molecular mediators of long-term memory such as BDNF and Arc are also modestly decreased resulting in mild to negligible memory impairments. In contrast, aged microglia exhibit immunological and morphological markers of activation (i.e., MHCII, CD11b, CD86), rendering them primed for a subsequent challenge. Upon a challenge, these microglia produce a potentiated neuroinflammatory response. Pro-inflammatory cytokine release is exaggerated and prolonged, lasting at least 8 days. Synaptic facilitation (LTP) and molecular mediators of long-term memory are profoundly reduced, and long-term contextual, and spatial memory is significantly impaired.