Hippocampal neuronal activity is aligned with action plans

Ipshita Zutshi, Athina Apostolelli, Wannan Yang, Zheyang Sam Zheng, Tora Dohi, Edoardo Balzani, Alex H. Williams, Cristina Savin and György Buzsáki ()
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Ipshita Zutshi: New York University Grossman School of Medicine
Athina Apostolelli: New York University Grossman School of Medicine
Wannan Yang: New York University Grossman School of Medicine
Zheyang Sam Zheng: New York University Grossman School of Medicine
Tora Dohi: New York University Grossman School of Medicine
Edoardo Balzani: New York University
Alex H. Williams: New York University
Cristina Savin: New York University
György Buzsáki: New York University Grossman School of Medicine

Nature, 2025, vol. 639, issue 8053, 153-161

Abstract: Abstract Neurons in the hippocampus are correlated with different variables, including space, time, sensory cues, rewards and actions, in which the extent of tuning depends on ongoing task demands1–8. However, it remains uncertain whether such diverse tuning corresponds to distinct functions within the hippocampal network or whether a more generic computation can account for these observations9. Here, to disentangle the contribution of externally driven cues versus internal computation, we developed a task in mice in which space, auditory tones, rewards and context were juxtaposed with changing relevance. High-density electrophysiological recordings revealed that neurons were tuned to each of these modalities. By comparing movement paths and action sequences, we observed that external variables had limited direct influence on hippocampal firing. Instead, spiking was influenced by online action plans and modulated by goal uncertainty. Our results suggest that internally generated cell assembly sequences are selected and updated by action plans towards deliberate goals. The apparent tuning of hippocampal neuronal spiking to different sensory modalities might emerge due to alignment to the afforded action progression within a task rather than representation of external cues.

Date: 2025
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DOI: 10.1038/s41586-024-08397-7

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