To confirm neural plasticity of the mouse hippocampo-prefrontal cortex (PFC) pathway, paired-pulse facilitation (PPF) and long-term potentiation (LTP) induction were determined in the pathway. In addition, we tested whether the plasticity differs in projections of the pathway from the dorsal (upper) and ventral (lower) parts of the temporal hippocampus. The results showed PPF and LTP of this pathway, and these differed between the projections. The projection from the upper part showed stronger PPF and weaker LTP compared with that from the lower part. These results suggest that the mouse hippocampo-PFC pathway is involved in learning and memory, and contains projections related to different functions.