〔Abstract〕 Objective To explore whether long-term potentiation(LTP) induced by brain-derived neurotrophic factor(BDNF) of hippocampus is involved in the process of maternal separation(MS) leading to impaired cognitive function of offspring in adolescence. Methods The newborn CD-1 mice were randomly divided into maternal separation group(MS group) and control group(CON group). Mice in MS group were separated from the mother mice for 3 h every day from postnatal day 4 to 21 while no intervention was taken in the CON group. The spatial learning and memory ability was assessed using Morris water maze at the age of 3 months. Western blot and real-time quantitative PCR were used to detect the levels of BDNF and BDNF mRNA in the hippocampus. LTP of the hippocampal CA3-CA1 neural pathway was recorded using electrophysiological techniques. Results Compared with CON group, the latency and distance of Morris water maze in maternal separation group were significantly longer(P<0.01). The percentage of time and distance in target quadrant during the memory phase in MS group were obviously lower than those in control group(P<0.05). The results of WB and Real-time quantitative PCR in MS group showed that the levels of BDNF and BDNF mRNA in MS group apparently decreased(P<0.05). Compared with CON group, MS group showed a significantly lower LTP in CA3-CA1 neural pathway(P<0.01). Conclusion The certain intensity of maternal separation can impair learning and memory function in young CD-1 male mice, which may be associated with decreased expression of BDNF and impaired LTP in the hippocampus.