The major experimental findings were summarized as the following: (1) HH exposure induces microglia activation, and synaptic loss, and causes memory loss in mice; (2) HH induces M1-type polarized microglia and activates CX3CL1/CX3CR1 signal; (3) CX3CR1- deficiency significantly attenuates microglial activation, synaptic loss, and memory impairment induced by HH; (4) hypoxia-induced microglia polarization was dependent on CX3CR1, and CX3CL1 exacerbated hypoxia-induced M1-type microglia; and (5) hypoxia-induced the uptake of synapses through the upregulation of microglial phagocytosis. Here, CX3CL1 is linked to memory impairment.