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bioRxiv · 10.64898/2026.05.20.726518

Hippocampus-reuniens beta coupling supports goal-directed spatial navigation

Baumann, T.·Mei, H.·Eschenko, O.
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Abstract

Prefrontal-hippocampal communication, supported by both direct and indirect anatomical pathways, is essential for a range of cognitive functions, including spatial navigation. The midline thalamic nucleus reuniens (RE) has been proposed as a key hub along this indirect pathway, coordinating bidirectional interactions between the hippocampus (HC) and prefrontal cortex (PFC). Here, we investigated functional dynamics within the HC-RE-PFC network as adult male rats learned to navigate a complex maze. Initial behavioral analyses revealed three distinct learning phases: exploration, goal-oriented learning, and efficient navigation. Aligning neural data with subject-specific transitions between these phases uncovered distinct neural signatures associated with each learning phase. Notably, the transition from exploratory to goal-directed behavior was accompanied by the emergence of persistent HC-RE beta-band (15-25Hz) interactions, including elevated beta coherence, theta-beta phase-amplitude coupling, and HC-to-RE Granger causality. The interactions further scaled with navigational efficiency, showing increased HC-RE beta coherence in trials without errors. Together, these findings provide new evidence for dynamic HC-RE interactions during goal-directed navigation and support an emerging view that RE functions as a working memory buffer for route-related information, revealing a potential network mechanism underlying flexible spatial behavior. HighlightsO_LIBeta-band hippocampus-reuniens coupling emerges during goal-directed navigation. C_LIO_LIPAC between HC theta and RE beta increased during goal learning. C_LIO_LIHC-RE coupling strength increases with navigational efficiency. C_LIO_LIDirectional hippocampus-to-reuniens communication emerges during learning C_LIO_LIReuniens supports hippocampal-prefrontal integration for flexible behavior C_LI Significance StatementFlexible spatial navigation requires coordinated communication between the hippocampus (HC) and the prefrontal cortex (PFC), yet the thalamic mechanisms coordinating HC-PFC interaction remain poorly understood. This study reveals that the nucleus reuniens (RE) of the midline thalamus plays a critical role in mediating HC-PFC communication during spatial learning. By combining detailed behavioral analysis with simultaneous multi-site electrophysiological recording, we identify beta-band HC-RE coupling as a neural signature of the transition from exploration to goal-directed navigation. The strength and directionality of this interaction tracked improvements in navigational efficiency, revealing a thalamic mechanism for integrating hippocampal output into prefrontal circuits. These findings highlight the RE as a working memory buffer for route-related information and advance our understanding of how thalamic hubs contribute to the circuit-level dynamics underlying flexible behavior.

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Baumann, T., Mei, H., Eschenko, O.. 2026-05-22. Hippocampus-reuniens beta coupling supports goal-directed spatial navigation. https://doi.org/10.64898/2026.05.20.726518

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