Microglia-dependent regulation of fear memory extinction

Traumatic events produce enduring memories that may be attenuated through extinction learning. Previous work has identified neuronal mechanisms underlying extinction learning that involve the remodeling or inhibition of neuronal ensembles (or engrams) that support the original fear memory. Here we identify a role for microglia in extinction learning in mice. We show that, during extinction, microglia are recruited to the soma and dendritic processes of fear engram neurons in the dentate gyrus. Interactions between microglia and somata mediate transient silencing of engram neurons. Inhibition of microglial recruitment to somata attenuated extinction-induced reductions in engram reactivity and slowed extinction. By contrast, interactions between microglia and dendritic processes promote engulfment of engram synapses and remodeling of engram neurons. Blocking complement signaling in engram neurons prevented extinction-induced engram neuron remodeling and slowed extinction. Together, these findings identify microglia as key regulators of fear engram expression and remodeling during extinction learning.