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Active dendritic integration as a mechanism for robust and precise grid cell firing

Abstract

Understanding how active dendrites are exploited for behaviorally relevant computations is a fundamental challenge in neuroscience. Grid cells in medial entorhinal cortex are an attractive model system for addressing this question, as the computation they perform is clear: they convert synaptic inputs into spatially modulated, periodic firing. Whether active dendrites contribute to the generation of the dual temporal and rate codes characteristic of grid cell output is unknown. We show that dendrites of medial entorhinal cortex neurons are highly excitable and exhibit a supralinear input–output function in vitro, while in vivo recordings reveal membrane potential signatures consistent with recruitment of active dendritic conductances. By incorporating these nonlinear dynamics into grid cell models, we show that they can sharpen the precision of the temporal code and enhance the robustness of the rate code, thereby supporting a stable, accurate representation of space under varying environmental conditions. Our results suggest that active dendrites may therefore constitute a key cellular mechanism for ensuring reliable spatial navigation.

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Figure 1: Supralinear synaptic integration in MEC principal neurons.
Figure 2: Supralinear integration and dendritic spikes depend on voltage-gated sodium (Nav) and NMDA receptor channels.
Figure 3: Engagement of active dendritic conductances in MECII principal neurons in vivo.
Figure 4: Plateau potentials suggest that active dendritic conductances are engaged in vivo.
Figure 5: Active dendrites in MECII neurons can enhance the robustness of the rate code of grid cell firing.
Figure 6: Active dendrites in MECII neurons can promote the precision of the temporal code of grid cell firing.

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Acknowledgements

We are grateful to P. Latham, A. Packer and S. Turaga for discussions and comments on the manuscript, and to S. Chun for assistance with histology. This work was supported by grants from the Wellcome Trust (M.H.), ERC (StG 678790 NEWRON to C.S.-H. and AdG 695709 DendriteCircuits to M.H.) and Gatsby Charitable Foundation (M.H.).

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C.S.-H., A.R. and M.H. designed experiments and wrote the manuscript. C.S.-H. performed computational modeling, contributed to in vitro electrophysiology experiments and performed data analysis; G.T. performed in vitro experiments and data analysis. L.A. assisted with computational modeling. T.B. contributed to in vitro experiments. B.A.C. contributed to in vitro electrophysiology experiments and helped write the manuscript. M.H. supervised the project.

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Correspondence to Christoph Schmidt-Hieber or Michael Häusser.

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The authors declare no competing financial interests.

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Schmidt-Hieber, C., Toleikyte, G., Aitchison, L. et al. Active dendritic integration as a mechanism for robust and precise grid cell firing. Nat Neurosci 20, 1114–1121 (2017). https://doi.org/10.1038/nn.4582

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