Inhibitory hippocampus-medial septum 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 regulating locomotion. However, the neuronal mechanisms of the hippocampal regulation of locomotion and exploratory behavior remain unclear. In this study, we found that the inhibitory hippocampal synaptic projection to the medial septum (MS) bi-directionally controls the locomotor speed of mice. The activation of the MS-projecting interneurons in the hippocampus or the activation of the hippocampus-originated inhibitory synaptic terminals in the MS decreased locomotion and exploratory behavior. On the other hand, the inhibition of the hippocampus-originated inhibitory synaptic terminals in the MS increased locomotion. Unlike the septal projecting interneurons, the activation of the hippocampal interneurons projecting to the retrosplenial cortex did not change animal locomotion. Therefore, this study reveals a specific long-range inhibitory synaptic output from the hippocampus to the medial septum in the regulation of animal locomotion.

Brain-wide circuit-specific targeting of astrocytes

“… 37 We first injected into the LS AAV-Dlx-SynaptoTAG, which traced the axonal and synaptic projections of GABAergic neurons. 38 Similar to previous reports, the most prominent downstream targets of LS are medial septum, diagonal band nucleus (NDB), lateral hypothalamus, and the CA3 region of the hippocampus ( Figures 5 A and 5D). In Ai9 mice when we used AAV-Dlx-tTA to induce the expression of NS1 to trans -complement YFV ΔNS1 -Cre, we detected tdTomato-positive astrocytes in the major synaptic targets of the LS ( Figures 5 B and 5E).…”

“… 26 Addgene 175275 pAAV-Dlx-SynaptoTAG Chen et al. 38 GenBank Accession #: OR725556, Addgene 210729 AAV1-Cre N/A Addgene, 105545-AAV1 Chemicals , peptides , and recombinant proteins Doxycycline hyclate food Inotiv TD.01306 Paraformaldehyde (PFA) Electron Microscopy Sciences 19210 Deposited data The raw data of microscopic images of brain sections and data used to plot the graphs This paper https://doi.org/10.5281/zenodo.10019905 Experimental models : Cell lines HEK293T cell ATCC CRL-3216 BHK-21 cells ATCC CCL-10 Experimental models : Organisms/strains Mouse: C57BL/6J The Jackson Laboratory 000664 Mouse: Ai9 The Jackson Laboratory 007909 Mouse: Ai6 The Jackson Laboratory 007906 Mouse: Calb2-Cre The Jackson Laboratory 010774 …”

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.…”