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OBJECTIVE Although the role of newly identified aquaporin 4 (AQP4) in water transport has been extensively in vestigated, little is known about its contribution to hippocampal synaptic plasticity and memory.Since it has been detected wide ly co-localized with glutamate transporter 1 (GLT-1) in astro cytes, we thus investigated whether AQP4 was implicated in long-term potentiation (LTP) and memory formation via GLT-1.METHODS Using tissue immunofluorescence double staining to measure coexpression of AQP4 and GLT-1.WB was employed to detect the expression of GLT-1.In vivo electrophysiological re cording method was established to record the PS, and TBS was developed for the induction of LTP.Contextual fear conditioning test was used to evaluate hippocampus-dependent memory.Golgi impregnation indicated the density of dendritic spines.Results:Our present study demonstrated that AQP4 deficiency impaired hippocampal LTP and hippocampus-dependent memory formation and this impairment was mediated by the down-regulation of GLT-1 expression/function in hippocampus in AQP4 knockout (KO) mice, since it could be rescued by ceftriaxone (Cef), a stimulator of GLT-1.CONCLUSION These results suggest that AQP4 functions as the modulator of synaptic plasticity and actively regulates learning and memory.