Inhibitory hippocampo-septal projection controls locomotion and exploratory behavior

Abstract

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.

Unilateral hippocampal stroke in freely behaving mice reveals sex differences in contralesional spreading depolarization and associated behavior

“…It may also be the case that strong depolarization of hippocampal neurons indirectly evokes locomotor activity. While not directly involved in inducing motor activity, the hippocampus can influence running speed 51,52 and regulate spatial memory 53 allowing for navigation strategies in space. A stroke model in freely behaving mice will now permit interrogation of how modulating behavior in the hyperacute period might feedback onto SD generation and stroke outcomes.…”