Abstract
Hippocampal theta oscillations support encoding of an animal's position during spatial navigation, yet longstanding questions about their impact on locomotion remain unanswered. Combining optogenetic control of hippocampal theta oscillations with electrophysiological recordings in mice, we show that hippocampal theta oscillations regulate locomotion. In particular, we demonstrate that their regularity underlies more stable and slower running speeds during exploration. More regular theta oscillations are accompanied by more regular theta-rhythmic spiking output of pyramidal cells. Theta oscillations are coordinated between the hippocampus and its main subcortical output, the lateral septum (LS). Chemo- or optogenetic inhibition of this pathway reveals its necessity for the hippocampal regulation of running speed. Moreover, theta-rhythmic stimulation of LS projections to the lateral hypothalamus replicates the reduction of running speed induced by more regular hippocampal theta oscillations. These results suggest that changes in hippocampal theta synchronization are translated into rapid adjustment of running speed via the LS.
Highlights
Hippocampal theta oscillations support encoding of an animal’s position during spatial navigation, yet longstanding questions about their impact on locomotion remain unanswered
By combining optogenetic control of hippocampal theta oscillations with axonal chemogenetic (DREADDs) or optogenetic inhibition of Hip–lateral septum (LS) pathway, as well as using optogenetic activation of LS–lateral hypothalamus (LH) projections, we show the role of Hip to LS (Hip–LS)–LH pathway in theta-rhythmic regulation of locomotion
To study the role of hippocampal theta oscillations in locomotion, we developed a preparation that enabled precise temporal control of hippocampal theta rhythm in freely behaving mice
Summary
Hippocampal theta oscillations support encoding of an animal’s position during spatial navigation, yet longstanding questions about their impact on locomotion remain unanswered. Theta-rhythmic stimulation of LS projections to the lateral hypothalamus replicates the reduction of running speed induced by more regular hippocampal theta oscillations. Hippocampal theta oscillations (5–12 Hz) accompany spatial navigation[1,2,3], yet there are longstanding questions open about the role of the hippocampus (Hip) and theta oscillations in locomotion[4,5] via rhythmic coordination of specific brain circuits. Theta oscillations accompany running and their frequency changes with running speed[8,9,10,11], studies using lesions or electrical stimulation have revealed a complex relationship between theta synchronization and motor output, suggesting contradictory roles for the hippocampal theta rhythm in locomotion[5,12,13]. By combining optogenetic control of hippocampal theta oscillations with axonal chemogenetic (DREADDs) or optogenetic (eNpHR3.0) inhibition of Hip–LS pathway, as well as using optogenetic activation of LS–LH projections, we show the role of Hip–LS–LH pathway in theta-rhythmic regulation of locomotion
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