AWAKE SHARP-WAVE RIPPLES AND THEIR COUPLING WITH PREFRONTAL ACTIVITY SUPPORT THE OPTIMIZATION OF NAVIGATION STRATEGIES DURING GOAL-DIRECTED SPATIAL LEARNING

Goal-directed spatial learning requires the gradual integration of spatial memories to improve navigation efficiency through the optimization of navigation strategies. This process depends on coordinated neural activity between hippocampus (HPC) and medial-prefrontal cortex (mPFC). Although evidence suggests that the mPFC integrates hippocampal spatial information to guide the selection of efficient navigation strategies, the mechanisms enabling HPC–mPFC communication during goal-directed spatial learning remain incompletely characterized, particularly with respect to the contribution of awake sharp-wave ripples (aSWRs). Hippocampal-aSWRs have been linked to memory retrieval and are temporally coupled with cortical activity, suggesting a potential role in supporting the selection of efficient navigation strategies. However, their contribution to optimizing navigation strategies during goal-directed spatial learning remains unclear.
To address this question, we simultaneously recorded local field potentials from the dorsal-HPC and mPFC in mice performing spatial and non-spatial versions of the Barnes maze. In the spatial task, the escape location was fixed and hidden, requiring the formation and use of a spatial memory (hidden-fixed Barnes maze; hfBM). In contrast, in the non-spatial task, the escape location was visible, cue-linked, and varied across trials (cue-variable Barnes maze; cvBM).
We found that aSWR incidence increased selectively during efficient strategies in the spatial hfBM task, and that temporal coupling between aSWRs and mPFC activity emerged exclusively under spatial learning demands. Moreover, hippocampal–prefrontal phase-locking strengthened when animals adopted efficient trajectories. Together, these findings demonstrate that aSWRs selectively support HPC–mPFC communication during spatial learning, providing a neural mechanism for the gradual optimization of navigation strategies.