Microglia regulate cognition and stress-related cognitive disorders

Microglia are the resident macrophages of the central nervous system (CNS). Under normal physiological conditions, microglia constantly monitor the microenvironment in the brain, survey neuronal and synaptic activity, and mainly exist in a resting state. Resting microglia regulate synaptic pruning, a process critical for the regulation of neuronal activity and synaptic plasticity. By mediating synaptic pruning, resting microglia play an important role in the regulation of cognition, such as learning and memory, including the modulation of memory strength, forgetfulness, and memory quality. As a response to stress, brain injury, or neuroinflammation, microglia become activated and increase in number. Activated microglia change to an amoeboid shape and secrete proteins such as cytokines, which can lead to cognitive deficits associated with stress, posttraumatic stress disorder (PTSD), anxiety, depression, and many other neurological or mental disorders. Stressful events can activate microglia which induce neuroinflammation through the secretion of proinflammatory cytokines and reduction of antiinflammatory cytokines that initiate further inflammation and immune responses. In addition, psychological stressor-induced microglia activation and neuroinflammation result in deficits in synaptic pruning, synaptic plasticity, and cognition. With a focus on the microglial role in stress, we review the studies investigating the role of resting microglia in synaptic plasticity and learning and memory, as well as how activated microglia modulate stress-related plasticity and learning and memory deficits. Besides summarizing signaling pathways involved in these processes, we also discuss the possibility of microglia ablation or inhibition of microglial proinflammatory signaling as a therapeutic to ameliorate stress-related cognitive deficits.