Inhibitory hippocampo-septal projection controls locomotion and exploratory behavior

Although the hippocampus is generally considered a cognitive center for spatial representation, learning and memory, increasing evidence supports its roles in regulation of locomotion. However, the neuronal mechanisms of hippocampal regulation of locomotion and exploratory behavior remain unclear. Here we found that the inhibitory hippocampo-septal projection bi-directionally controls locomotion speed of mice. Pharmacogenetic activation of these septum-projecting interneurons decreased locomotion and exploratory behavior. Similarly, activation of the hippocampus-originated inhibitory terminal in the medial septum reduced locomotion. On the other hand, inhibition of the hippocampus-originated inhibitory terminal increased locomotion. The locomotion-regulative roles were specific to the septal projecting interneurons as activation of hippocampal interneurons projecting to the retrosplenial cortex did not change animal locomotion. Therefore, this study reveals a specific long-range inhibitory output from the hippocampus in the regulation of animal locomotion.