The entorhinal cortex contains neurons that represent self-location, including grid cells that fire in periodic locations and velocity signals that encode running speed and head direction. Although the size and shape of the environment influence grid patterns, whether entorhinal velocity signals are equally influenced or provide a universal metric for self-motion across environments remains unknown. Here we report that speed cells rescale after changes to the size and shape of the environment. Moreover, head direction cells reorganize in an experience-dependent manner to align with the axis of environmental change. A knockout mouse model allows dissociation of the coordination between cell types, with grid and speed cells, but not head direction cells, responding in concert to environmental change. These results point to malleability in the coding features of multiple entorhinal cell types and have implications for which cell types contribute to the velocity signal used by computational models of grid cells.
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Data that support the findings of this study are available from the corresponding authors upon reasonable request.
Code used in the analyses described in this manuscript can be accessed at: https://github.com/GiocomoLab/Munn_et_al_2019. The code used in the LNP model can be accessed at https://github.com/GiocomoLab/ln-model-of-mec-neurons
Hafting, T., Fyhn, M., Molden, S., Moser, M. B. & Moser, E. I. Microstructure of a spatial map in the entorhinal cortex. Nature 436, 801–806 (2005).
McNaughton, B. L., Battaglia, F. P., Jensen, O., Moser, E. I. & Moser, M. B. Path integration and the neural basis of the ‘cognitive map’. Nat. Rev. Neurosci. 7, 663–678 (2006).
Kropff, E., Carmichael, J. E., Moser, M. B. & Moser, E. I. Speed cells in the medial entorhinal cortex. Nature 523, 419–424 (2015).
Hinman, J. R., Brandon, M. P., Climer, J. R., Chapman, G. W. & Hasselmo, M. E. Multiple running speed signals in medial entorhinal cortex. Neuron 91, 666–679 (2016).
Hardcastle, K., Maheswaranathan, N., Ganguli, S. & Giocomo, L. M. A multiplexed, heterogeneous, and adaptive code for navigation in medial entorhinal cortex. Neuron 94, 375–387 (2017).
Sargolini, F. et al. Conjunctive representation of position, direction, and velocity in entorhinal cortex. Science 312, 758–762 (2006).
Stensola, T., Stensola, H., Moser, M. B. & Moser, E. I. Shearing-induced asymmetry in entorhinal grid cells. Nature 518, 207–212 (2015).
Krupic, J., Bauza, M., Burton, S., Barry, C. & O’Keefe, J. Grid cell symmetry is shaped by environmental geometry. Nature 518, 232–235 (2015).
Barry, C., Hayman, R., Burgess, N. & Jeffery, K. J. Experience-dependent rescaling of entorhinal grids. Nat. Neurosci. 10, 682–684 (2007).
Stensola, H. et al. The entorhinal map is discretized. Nature 492, 72–78 (2012).
Keinath, A. T., Epstein, R. A. & Balasubramanian, V. Environmental deformations dynamically shift the grid cell spatial metric. eLife 7, e38169 (2018).
Campbell, M. G. et al. Principles governing the integration of landmark and self-motion cues in entorhinal cortical codes for navigation. Nat. Neurosci. 21, 1096–1106 (2018).
Campbell, M. G. & Giocomo, L. M. Self-motion processing in visual and entorhinal cortices: inputs, integration and implications for position coding. J. Neurophysiol. 120, 2091–2106 (2018).
Fuhs, M. C. & Touretzky, D. S. A spin glass model of path integration in rat medial entorhinal cortex. J. Neurosci. 26, 4266–4276 (2006).
Guanella, A., Kiper, D. & Verschure, P. A model of grid cells based on a twisted torus topology. Int. J. Neural Syst. 17, 231–240 (2007).
Burak, Y. & Fiete, I. R. Accurate path integration in continuous attractor network models of grid cells. PLoS Comput. Biol. 5, e1000291 (2009).
Pastoll, H., Solanka, L., van Rossum, M. C. & Nolan, M. F. Feedback inhibition enables θ-nested γ oscillations and grid firing fields. Neuron 77, 141–154 (2013).
Burgess, N., Barry, C. & O’Keefe, J. An oscillatory interference model of grid cell firing. Hippocampus 17, 801–812 (2007).
Burgess, N. Grid cells and theta as oscillatory interference: theory and predictions. Hippocampus 18, 1157–1174 (2008).
Giocomo, L. M., Zilli, E. A., Fransen, E. & Hasselmo, M. E. Temporal frequency of subthreshold oscillations scales with entorhinal grid cell field spacing. Science 315, 1719–1722 (2007).
Welday, A. C., Shlifer, I. G., Bloom, M. L., Zhang, K. & Blair, H. T. Cosine directional tuning of theta cell burst frequencies: evidence for spatial coding by oscillatory interference. J. Neurosci. 31, 16157–16176 (2011).
Couey, J. J. et al. Recurrent inhibitory circuitry as a mechanism for grid formation. Nat. Neurosci. 16, 318–324 (2013).
Hasselmo, M. E., Giocomo, L. M. & Zilli, E. A. Grid cell firing may arise from interference of theta frequency membrane potential oscillations in single neurons. Hippocampus 17, 1252–1271 (2007).
Bush, D. & Burgess, N. A hybrid oscillatory interference/continuous attractor network model of grid cell firing. J. Neurosci. 34, 5065–5079 (2014).
Raudies, F. & Hasselmo, M. E. Differences in visual–spatial input may underlie different compression properties of firing fields for grid cell modules in medial entorhinal cortex. PLoS Comput. Biol. 11, e1004596 (2015).
Giocomo, L. M. et al. Grid cells use HCN1 channels for spatial scaling. Cell 147, 1159–1170 (2011).
Mallory, C. S., Hardcastle, K., Bant, J. S. & Giocomo, L. M. Grid scale drives the scale and long-term stability of place maps. Nat. Neurosci. 21, 270–282 (2018).
Jeewajee, A., Barry, C., O’Keefe, J. & Burgess, N. Grid cells and theta as oscillatory interference: electrophysiological data from freely moving rats. Hippocampus 18, 1175–1185 (2008).
Xu, C., Datta, S., Wu, M. & Alreja, M. Hippocampal theta rhythm is reduced by suppression of the H-current in septohippocampal GABAergic neurons. Eur. J. Neurosci. 19, 2299–2309 (2004).
Kocsis, B. & Li, S. In vivo contribution of H channels in the septal pacemaker to theta rhythm generation. Eur. J. Neurosci. 20, 2149–2158 (2004).
Lewis, A. S. et al. Deletion of the hyperpolarization-activated cyclic nucleotide-gated channel auxiliary subunit TRIP8b impairs hippocampal Ih localization and function and promotes antidepressant behavior in mice. J. Neurosci. 31, 7424–7440 (2011).
Mhatre, H., Gorchetchnikov, A. & Grossberg, S. Grid cell hexagonal patterns formed by fast self-organizing learning within entorhinal cortex. Hippocampus 22, 320–334 (2012).
Hasselmo, M. E. & Brandon, M. P. A model combining oscillations and attractor dynamics for generation of grid cell firing. Front. Neural Circuits 6, 30 (2012).
Raudies, F., Brandon, M. P., Chapman, G. W. & Hasselmo, M. E. Head direction is coded more strongly than movement direction in a population of entorhinal neurons. Brain Res. 621, 355–367 (2015).
Zutshi, I. et al. Recurrent circuits within medial entorhinal cortex superficial layer support grid cell firing. Nat. Commun. 9, 3701 (2018).
Zutshi, I., Leutgeb, J. K. & Leutgeb, S. Theta sequences of grid cell populations can provide a movement-direction signal. Curr. Opn. Behav. Sci. 17, 147–154 (2017).
Blair, H. T., Cho, J. & Sharp, P. E. Role of the lateral mammillary nucleus in the rat head direction circuit: a combined single unit recording and lesion study. Neuron 21, 1387–1397 (1998).
Blair, H. T. & Sharp, P. E. Anticipatory head direction signals in anterior thalamus: evidence for a thalamocortical circuit that integrates angular head motion to compute head direction. J. Neurosci. 9, 6260–6270 (1995).
Krupic, J., Bauza, M., Burton, S., Lever, C. & O’Keefe, J. How environment geometry affects grid cell symmetry and what we can learn from it. Philos. Trans. R. Soc. B 369, 20130188 (2014).
Ocko, S. A., Hardcastle, K., Giocomo, L. M. & Ganguli, S. Emergent elasticity in the neural code for space. Proc. Natl Acad. Sci. USA 115, E11798–E11806 (2018).
Park, E. H., Keeley, S., Ranck, J. B. Jr. & Fenton, A. A. How the internally-organized direction sense is used to navigate. Neuron 101, 1–9 (2018).
Jacob, P.-Y. et al. An independent, landmark-dominated head-direction signal in dysgranular retrosplenial cortex. Nat. Neurosci. 20, 173–175 (2017).
Perez-Escobar, J. A., Kornienko, O., Latuske, P., Kohler, L. & Allen, K. Visual landmarks sharpen grid cell metric and confer context specificity to neurons of the medial entorhinal cortex. eLife 23, e16937 (2016).
Raudies, F., Mingolla, E. & Hasselmo, M. E. Modeling the influence of optic flow on grid cell firing in the absence of other cues. J. Comput. Neurosci. 33, 475–493 (2012).
Garden, D. L., Dodson, P. D., O’Donnell, C., White, M. D. & Nolan, M. F. Tuning of synaptic integration in the medial entorhinal cortex to the organization of grid cell firing fields. Neuron 60, 875–889 (2008).
Justus, D. et al. Glutamatergic synaptic integration of locomotion speed via septoentorhinal projections. Nat. Neurosci. 20, 16–19 (2017).
Andermann, M. L., Kerlin, A. M., Roumis, D. K., Glickfeld, L. L. & Reid, R. C. Functional specialization of mouse higher visual cortical areas. Neuron 72, 1025–1039 (2011).
Wang, Q., Gao, E. & Burkhalter, A. Gateways of ventral and dorsal streams in mouse visual cortex. J. Neurosci. 31, 1905–1918 (2011).
Saleem, A. B., Ayaz, A., Jeffery, K. J., Harris, K. D. & Carandini, M. Integration of visual motion and locomotion in mouse visual cortex. Nat. Neurosci. 16, 1864–1869 (2013).
Pan, Y. et al. TRIP8b is required for maximal expression of HCN1 in the mouse retina. PLoS One 9, e85850 (2014).
Schmitzer-Tobert, N., Jackson, J., Henze, D., Harris, K. & Redish, A. D. Quantitative measures of cluster quality for use in extracellular recordings. Neuroscience 131, 1–11 (2005).
Skaggs, W. E., McNaughton, B. L., Wilson, M. A. & Barnes, C. A. Theta phase precession in hippocampal neuronal populations and the compression of temporal sequences. Hippocampus 6, 149–172 (1996).
Franklin, K. B. J. & Paxinos, G. The Mouse Brain in Stereotaxic Coordinates 3rd ed (Academic Press, 2007).
Langston, R. F. et al. Development of the spatial representation system in the rat. Science 328, 1576–1580 (2010).
Wills, T. J., Cacucci, F., Burgess, N. & O’Keefe, J. Development of the hippocampal cognitive map in preweanling rats. Science 328, 1573–1576 (2010).
Fitzgibbon, A., Pilu, M. & Fisher, R. B. Direct least square fitting of ellipses. IEEE Transactions on Pattern Analysis and Machine Intelligence 21, 476-480 (1999).
Berens, P. CircStat: a MATLAB toolbox for circular statistics. J. Stat. Softw. 31, 1–21 (2009).
Zar, J. H. Biostatistical Analysis (Prentice Hall, 1999).
L.M.G. recieves funding as a New York Stem Cell Foundation–Robertson Investigator. This work was supported by funding from the New York Stem Cell Foundation, NIMH MH106475, the Office of Naval Research N000141812690, the Simons Foundation 542987SPI, the Whitehall Foundation, the James S. McDonnell Foundation and a Klingenstein–Simons award to L.M.G.; the Philip Wrightson Postdoctoral Fellowship from the Neurological Foundation of New Zealand awarded to R.G.M.; a National Science Foundation Graduate Research Fellowship awarded to C.S.M; a Stanford Interdiscplinary Graduate Fellowship awarded to K.H.; and NINDS NS059934 to D.M.C. We thank A. Borrayo and A. Diaz for histology assistance and M.E. Hasselmo for input on the oscillatory interference model.
The authors declare no competing interests.
Peer review information Nature Neuroscience thanks Dori Derdikman and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Munn, R.G.K., Mallory, C.S., Hardcastle, K. et al. Entorhinal velocity signals reflect environmental geometry. Nat Neurosci (2020). https://doi.org/10.1038/s41593-019-0562-5