Involvement of microglia in disturbed fear memory regulation: Possible microglial contribution to the pathophysiology of posttraumatic stress disorder

Microglia, immune cells in the brain, play a crucial role in brain inflammation and synaptic plasticity by releasing inflammatory mediators and neurotrophic factors as well as, phagocytosing synaptic elements. Recent studies have shown peripheral inflammation, immune alteration in the brain are associated with post-traumatic stress disorder (PTSD) in humans. Several preclinical studies using Pavlovian fear conditioning have suggested that microglia are involved in fear memory dysregulation and altered fear neuronal networks. Microglial priming resulting from previous stressful experiences may also have an effect. This review will introduce the current knowledge of microglial contribution to disturbed fear memory regulation, a fundamental feature of PTSD. •・Microglia can act on fear memory circuits through various mediators or phagocytosis.•・Stressful experiences influences microglia in the long term.•・Previous studies suggest microglial alterations engage in fear memory dysregulation.•・We hypothesize prior stressors cause microglia to respond to a trauma maladaptively.