Principles governing the integration of landmark and self-motion cues in entorhinal cortical codes for navigation

Abstract

To guide navigation, the nervous system integrates multisensory self-motion and landmark information. We dissected how these inputs generate spatial representations by recording entorhinal grid, border and speed cells in mice navigating virtual environments. Manipulating the gain between the animal’s locomotion and the visual scene revealed that border cells responded to landmark cues while grid and speed cells responded to combinations of locomotion, optic flow and landmark cues in a context-dependent manner, with optic flow becoming more influential when it was faster than expected. A network model explained these results by revealing a phase transition between two regimes in which grid cells remain coherent with or break away from the landmark reference frame. Moreover, during path-integration-based navigation, mice estimated their position following principles predicted by our recordings. Together, these results provide a theoretical framework for understanding how landmark and self-motion cues combine during navigation to generate spatial representations and guide behavior.

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Fig. 1: Functionally identified MEC cell types in real and virtual environments.
Fig. 2: Gain manipulations place visual and locomotor cues in conflict.
Fig. 3: Structural analyses of gain change responses reveal an asymmetry in the weighting of visual and locomotor cues by grid cells.
Fig. 4: Gain-dependent integration of visual and locomotor cues by speed cells.
Fig. 5: A coupled-oscillator attractor network model of the integration of landmarks and self-motion input by grid cells.
Fig. 6: Grid cell responses to an intermediate gain value follow the predictions of the model.
Fig. 7: Integration of visual and locomotor cues in a path integration task.

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Acknowledgements

We thank A. Borrayo and A. Diaz for histology assistance, C. Moffatt for help collecting electrophysiological data, and C. Kim, C. Bennett and S. Hestrin for help setting up the VR system. L.M.G. is a New York Stem Cell Foundation – Robertson Investigator. This work was supported by funding from the New York Stem Cell Foundation, Whitehall Foundation, NIMH MH106475, an Office of Naval Research Young Investigator Program Award and a Klingenstein-Simons award to L.M.G., funding from the Simons Foundation, James S McDonnell Foundation awarded to L.M.G. and S.G., funding from the McKnight Foundation and Burroughs Wellcome Foundation to S.G., an NSF Graduate Research Fellowship and Baxter Fellowship awarded to M.G.C., a Karel Urbanek Postdoctoral Fellowship in Applied Physics awarded to S.A.O., an NSF Graduate Research Fellowship awarded to C.S.M. and funding from T32 MH020016 for I.I.C.L.

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L.M.G. and M.G.C. conceived experiments and analyses. C.S.M. and M.G.C. performed chronic implantations and M.G.C. collected and analyzed in vivo data. M.G.C. and I.I.C.L. collected behavioral data. S.A.O. and S.G. conceived modeling and simulations and S.A.O. performed them. L.M.G. and M.G.C. wrote the paper with feedback from all authors.

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Correspondence to Malcolm G. Campbell or Lisa M. Giocomo.

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Supplementary Video 1 - Mouse performing path integration task.

The video shows three trials of the task. In the first two trials, the animal was given a water reward after running 200 cm following the onset of the visual cues. In the third trial, the reward was omitted, but the animal slowed down in the location it usually received a reward. This spontaneous slowing behavior was used to estimate the animal’s perceived location on the track. Black and white squares on the floor, ceiling and walls were randomized each trial so that they could not be used as landmarks. The length of the intertrial interval was randomized each trial (30–130 cm)

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Campbell, M.G., Ocko, S.A., Mallory, C.S. et al. Principles governing the integration of landmark and self-motion cues in entorhinal cortical codes for navigation. Nat Neurosci 21, 1096–1106 (2018). https://doi.org/10.1038/s41593-018-0189-y

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