Goal-directed hippocampal theta sweeps during memory-guided navigation

Abstract During navigation, animals continually sample their surrounding space and plan routes to distant goals. The brain mechanisms underlying these behaviors and how they coordinate to support memory-guided navigation in open environments are not understood. Using large-scale recordings in rats, we found two distinct types of place cell sequences within theta cycles that encoded trajectories sweeping beyond the animal’s location: stereotypic left-right alternating sweeps and learning-dependent goal-directed sweeps. Goal-directed sweeps predicted upcoming trajectories to remembered goal locations, were coordinated with prefrontal cortex activity and preferentially replayed during sharp-wave ripples. We further describe a circuit mechanism in which a subpopulation of CA1 cells encodes egocentric goal direction, combined with reduced feedback inhibition, to generate goal-directed theta sweeps. These results indicate a flexible mechanism to support different behavioral demands during navigation. Competing Interest Statement The authors have declared no competing interest. Footnotes Main text and supplementary materials received minor updates throughout.