Recurrent circuits within medial entorhinal cortex superficial layers support grid cell firing
Open accessAbstract
Specialized cells in the medial entorhinal cortex (mEC), such as speed cells, head direction (HD) cells, and grid cells, are thought to support spatial navigation. To determine whether these computations are dependent on local circuits, we record neuronal activity in mEC layers II and III and optogenetically perturb locally projecting layer II pyramidal cells. We find that sharply tuned HD cells are only weakly responsive while speed, broadly tuned HD cells, and grid cells show pronounced transient excitatory and inhibitory responses. During the brief period of feedback inhibition, there is a reduction in specifically grid accuracy, which is corrected as firing rates return to baseline. These results suggest that sharp HD cells are embedded in a separate mEC sub-network from broad HD cells, speed cells, and grid cells. Furthermore, grid tuning is not only dependent on local processing but also rapidly updated by HD, speed, or other afferent inputs to mEC.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Spike downsampling was implemented by randomly removing spikes during immobility periods from behaviorally-modulated units to match the median firing rate of non-modulated units.
“Spike downsampling was implemented by randomly removing spikes during immobility periods from behaviorally-modulated units to match the median firing rate of non-modulated units (Supplementary Figs. 6b and 3g)135,136.”
From Place and behavioral modulation of hippocampal neurons during immobility (2026) · cites this paper as [136]
The Methods section (“Measuring effects of optical stimulation: Speed tuning”; page unavailable) describes randomly selecting spikes before light onset to match the number of spikes during maximal inhibition. It does not describe removing spikes during immobility from behaviorally modulated units or matching the median firing rate of non-modulated units. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Fiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890 · see citing works
Microstructure of a spatial map in the entorhinal cortex
Hafting, T., Fyhn, M., Molden, S., Moser, M.-B., & Moser, E. I. (2005) · Nature · doi:10.1038/nature03721 · Cited by 4,068 · see citing works
Path integration and the neural basis of the 'cognitive map'
McNaughton, B. L., Battaglia, F. P., Jensen, O., Moser, E. I., & Moser, M.-B. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1932 · Cited by 2,024 · see citing works
Taube, J., Muller, R., & Ranck, J. (1990) · The Journal of Neuroscience · doi:10.1523/jneurosci.10-02-00420.1990 · Cited by 1,809 · see citing works
Conjunctive Representation of Position, Direction, and Velocity in Entorhinal Cortex
Sargolini, F., Fyhn, M., Hafting, T., McNaughton, B. L., Witter, M. P., Moser, M.-B., & Moser, E. I. (2006) · Science · doi:10.1126/science.1125572 · Cited by 1,485 · see citing works
Awake hippocampal sharp-wave ripples support spatial memory
Jadhav, S. P., Kemere, C., German, P. W., & Frank, L. M. (2012) · Science · doi:10.1126/science.1217230 · Cited by 924 · see citing works
The Head Direction Signal: Origins and Sensory-Motor Integration
Taube, J. S. (2007) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.112854 · Cited by 916 · see citing works
Disruption of ripple‐associated hippocampal activity during rest impairs spatial learning in the rat
Ego‐Stengel, V., & Wilson, M. A. (2010) · Hippocampus · doi:10.1002/hipo.20707 · Cited by 842 · see citing works
Accurate Path Integration in Continuous Attractor Network Models of Grid Cells
Burak, Y., & Fiete, I. R. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000291 · Cited by 779 · see citing works
Control of timing, rate and bursts of hippocampal place cells by dendritic and somatic inhibition
Royer, S., Zemelman, B. V., Losonczy, A., Kim, J., Chance, F., Magee, J. C., & Buzsáki, G. (2012) · Nature Neuroscience · doi:10.1038/nn.3077 · Cited by 728 · see citing works
The entorhinal grid map is discretized
Stensola, H., Stensola, T., Solstad, T., Frøland, K., Moser, M., & Moser, E. I. (2012) · Nature · doi:10.1038/nature11649 · Cited by 702 · see citing works
An oscillatory interference model of grid cell firing
Burgess, N., Barry, C., & O'Keefe, J. M. (2007) · Hippocampus · doi:10.1002/hipo.20327 · Cited by 688 · see citing works
Speed cells in the medial entorhinal cortex
Kropff, E., Carmichael, J. E., Moser, M.-B., & Moser, E. I. (2015) · Nature · doi:10.1038/nature14622 · Cited by 668 · see citing works
Quantitative measures of cluster quality for use in extracellular recordings
Schmitzer-Torbert, N. C., Jackson, J. C., Henze, D. A., Harris, K., & Redish, A. D. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2004.09.066 · Cited by 642 · see citing works
A Spin Glass Model of Path Integration in Rat Medial Entorhinal Cortex
Fuhs, M. C., & Touretzky, D. S. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4353-05.2006 · Cited by 628 · see citing works
Alonso, A., & Klink, R. (1993) · Journal of Neurophysiology · doi:10.1152/jn.1993.70.1.128 · Cited by 421 · see citing works
Recurrent inhibitory circuitry as a mechanism for grid formation
Couey, J. J., Witoelar, A., Zhang, S., Zheng, K., Ye, J., Dunn, B. A., Czajkowski, R., Moser, M., Moser, E. I., Roudi, Y., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3310 · Cited by 413 · see citing works
Divergent routing of positive and negative information from the amygdala during memory retrieval
Beyeler, A., Namburi, P., Glober, G. F., Simonnet, C., Calhoon, G. G., Conyers, G. F., Luck, R., Wildes, C. P., & Tye, K. M. (2016) · Neuron · doi:10.1016/j.neuron.2016.03.004 · Cited by 412 · see citing works
Reduction of Theta Rhythm Dissociates Grid Cell Spatial Periodicity from Directional Tuning
Brandon, M. P., Bogaard, A. R., Libby, C. P., Connerney, M. A., Gupta, K., & Hasselmo, M. E. (2011) · Science · doi:10.1126/science.1201652 · Cited by 407 · see citing works
Optetrode: a multichannel readout for optogenetic control in freely moving mice
Anikeeva, P., Andalman, A. S., Witten, I. B., Warden, M. R., Goshen, I., Grosenick, L., Gunaydin, L. A., Frank, L. M., & Deisseroth, K. A. (2011) · Nature Neuroscience · doi:10.1038/nn.2992 · Cited by 381 · see citing works
The Spatial Periodicity of Grid Cells Is Not Sustained During Reduced Theta Oscillations
Koenig, J., Linder, A. N., Leutgeb, J. K., & Leutgeb, S. (2011) · Science · doi:10.1126/science.1201685 · Cited by 378 · see citing works
Self-citationGrid cell symmetry is shaped by environmental geometry
Krupic, J., Bauža, M., Burton, S., Barry, C., & O'Keefe, J. M. (2015) · Nature · doi:10.1038/nature14153 · Cited by 372 · see citing works
Grid cells require excitatory drive from the hippocampus
Bonnevie, T., Dunn, B. A., Fyhn, M., Hafting, T., Derdikman, D., Kubie, J. L., Roudi, Y., Moser, E. I., & Moser, M. (2013) · Nature Neuroscience · doi:10.1038/nn.3311 · Cited by 341 · see citing works
Island Cells Control Temporal Association Memory
北村, 貴., Pignatelli, M., Suh, J., Kohara, K., Yoshiki, A., Abe, K., & Tonegawa, S. (2014) · Science · doi:10.1126/science.1244634 · Cited by 327 · see citing works
Membrane potential dynamics of grid cells
Domnisoru, C., Kinkhabwala, A. A., & Tank, D. W. (2013) · Nature · doi:10.1038/nature11973 · Cited by 309 · see citing works
Feedback Inhibition Enables Theta-Nested Gamma Oscillations and Grid Firing Fields
Pastoll, H., Solanka, L., van Rossum, M. C. W., & Nolan, M. F. (2013) · Neuron · doi:10.1016/j.neuron.2012.11.032 · Cited by 278 · see citing works
Cellular mechanisms of spatial navigation in the medial entorhinal cortex
Schmidt‐Hieber, C., & Häusser, M. (2013) · Nature Neuroscience · doi:10.1038/nn.3340 · Cited by 273 · see citing works
van Groen, T., & Wyss, J. M. (1990) · Brain Research · doi:10.1016/0006-8993(90)90824-u · Cited by 254 · see citing works
Disruption of the head direction cell network impairs the parahippocampal grid cell signal
Winter, S. S., Clark, B. J., & Taube, J. S. (2015) · Science · doi:10.1126/science.1259591 · Cited by 247 · see citing works
Computational Models of Grid Cells
Giocomo, L. M., Moser, M., & Moser, E. I. (2011) · Neuron · doi:10.1016/j.neuron.2011.07.023 · Cited by 231 · see citing works
Target-selective GABAergic control of entorhinal cortex output
Varga, C., Lee, S. Y., & Soltesz, I. (2010) · Nature Neuroscience · doi:10.1038/nn.2570 · Cited by 219 · see citing works
Grid cells and theta as oscillatory interference: Electrophysiological data from freely moving rats
Jeewajee, A., Barry, C., O'Keefe, J., & Burgess, N. (2008) · Hippocampus · doi:10.1002/hipo.20510 · Cited by 212 · see citing works
Hasselmo, M. E. (2008) · Hippocampus · doi:10.1002/hipo.20512 · Cited by 209 · see citing works
Diehl, G. W., Hon, O. J., Leutgeb, S., & Leutgeb, J. K. (2017) · Neuron · doi:10.1016/j.neuron.2017.03.004 · Cited by 204 · see citing works
Self-citationLocal and Distant Input Controlling Excitation in Layer II of the Medial Entorhinal Cortex
Fuchs, E. C., Neitz, A., Pinna, R., Melzer, S., Caputi, A., & Monyer, H. (2015) · Neuron · doi:10.1016/j.neuron.2015.11.029 · Cited by 179 · see citing works
Laminar differences in recurrent excitatory transmission in the rat entorhinal cortex in vitro
Dhillon, A., & Jones, R. S. G. (2000) · Neuroscience · doi:10.1016/s0306-4522(00)00225-6 · Cited by 171 · see citing works
Absence of Visual Input Results in the Disruption of Grid Cell Firing in the Mouse
Chen, G., Manson, D., Cacucci, F., & Wills, T. J. (2016) · Current Biology · doi:10.1016/j.cub.2016.06.043 · Cited by 167 · see citing works
Buetfering, C., Allen, K., & Monyer, H. (2014) · Nature Neuroscience · doi:10.1038/nn.3696 · Cited by 160 · see citing works
Grid Cells Use HCN1 Channels for Spatial Scaling
Giocomo, L. M., Hussaini, S. A., Fan, Z., Kandel, E. R., Moser, M., & Moser, E. I. (2011) · Cell · doi:10.1016/j.cell.2011.08.051 · Cited by 158 · see citing works
Entorhinal Cortical Ocean Cells Encode Specific Contexts and Drive Context-Specific Fear Memory
北村, 貴., Sun, C., Martin, J., Kitch, L. J., Schnitzer, M. J., & Tonegawa, S. (2015) · Neuron · doi:10.1016/j.neuron.2015.08.036 · Cited by 156 · see citing works
Multiple Running Speed Signals in Medial Entorhinal Cortex
Hinman, J. R., Brandon, M. P., Climer, J. R., Chapman, G. W., & Hasselmo, M. E. (2016) · Neuron · doi:10.1016/j.neuron.2016.06.027 · Cited by 156 · see citing works
Topography of Head Direction Cells in Medial Entorhinal Cortex
Giocomo, L. M., Stensola, T., Bonnevie, T., Cauter, T. V., Moser, M., & Moser, E. I. (2014) · Current Biology · doi:10.1016/j.cub.2013.12.002 · Cited by 142 · see citing works
Canto, C. B., & Witter, M. P. (2011) · Hippocampus · doi:10.1002/hipo.20997 · Cited by 141 · see citing works
Canto, C. B., & Witter, M. P. (2011) · Hippocampus · doi:10.1002/hipo.20993 · Cited by 137 · see citing works
Miao, C., Cao, Q., Moser, M., & Moser, E. I. (2017) · Cell · doi:10.1016/j.cell.2017.08.050 · Cited by 129 · see citing works
Sürmeli, G., Marcu, D.-C., McClure, C., Garden, D. L. F., Pastoll, H., & Nolan, M. F. (2015) · Neuron · doi:10.1016/j.neuron.2015.10.041 · Cited by 127 · see citing works
Spike phase precession persists after transient intrahippocampal perturbation
Zugaro, M., Monconduit, L., & Buzsáki, G. (2004) · Nature Neuroscience · doi:10.1038/nn1369 · Cited by 125 · see citing works
Distinct speed dependence of entorhinal island and ocean cells, including respective grid cells
Sun, C., 北村, 貴., Yamamoto, J., Martin, J., Pignatelli, M., Kitch, L. J., Schnitzer, M. J., & Tonegawa, S. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1511668112 · Cited by 120 · see citing works
Intervening inhibition underlies simple-cell receptive field structure in visual cortex
Liu, B., Li, P., Sun, Y. J., Li, Y.-T., Zhang, L. I., & Tao, H. W. (2009) · Nature Neuroscience · doi:10.1038/nn.2443 · Cited by 120 · see citing works
Layer 4 fast-spiking interneurons filter thalamocortical signals during active somatosensation
Yu, J., Gutnisky, D. A., Hires, S. A., & Svoboda, K. (2016) · Nature Neuroscience · doi:10.1038/nn.4412 · Cited by 111 · see citing works
Models of Grid Cell Spatial Firing Published 2005–2011
Zilli, E. A. (2012) · Frontiers in Neural Circuits · doi:10.3389/fncir.2012.00016 · Cited by 105 · see citing works
Tang, Q., Burgalossi, A., Ebbesen, C. L., Ray, S., Naumann, R. K., Schmidt, H., Spicher, D., & Brecht, M. (2014) · Neuron · doi:10.1016/j.neuron.2014.11.009 · Cited by 102 · see citing works
Kanter, B. R., Lykken, C. M., Avesar, D., Weible, A. P., Dickinson, J. R., Dunn, B. A., Borgesius, N. Z., Roudi, Y., & Kentros, C. G. (2017) · Neuron · doi:10.1016/j.neuron.2017.03.001 · Cited by 100 · see citing works
In vivo optogenetic identification and manipulation of GABAergic interneuron subtypes
Roux, L., Stark, E., Sjulson, L., & Buzsáki, G. (2014) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.12.013 · Cited by 83 · see citing works
Excitatory Microcircuits within Superficial Layers of the Medial Entorhinal Cortex
Winterer, J., Maier, N., Wozny, C., Beed, P. S., Breustedt, J., Evangelista, R., Peng, Y., D’Albis, T., Kempter, R., & Schmitz, D. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.04.041 · Cited by 82 · see citing works
Functional connectivity of the entorhinal–hippocampal space circuit
Zhang, S., Ye, J., Couey, J. J., Witter, M. P., Moser, E. I., & Moser, M. (2013) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2012.0516 · Cited by 58 · see citing works
Grid cell spatial tuning reduced following systemic muscarinic receptor blockade
Newman, E. L., Climer, J. R., & Hasselmo, M. E. (2014) · Hippocampus · doi:10.1002/hipo.22253 · Cited by 50 · see citing works
Number estimates of neuronal phenotypes in layer II of the medial entorhinal cortex of rat and mouse
Gatome, C. W., Slomianka, L., Lipp, H., & Amrein, I. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.06.048 · Cited by 50 · see citing works
A test of the reverberatory activity hypothesis for hippocampal ‘place’ cells
Moser, E. I., Moser, M., Lipa, P., Newton, M., Houston, F. P., Barnes, C. A., & McNaughton, B. L. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.09.044 · Cited by 17 · see citing works
Huntington’s Disease: Nuclear Gatekeepers Under Attack
Veldman, M. B., & Yang, X. W. (2017) · Neuron · doi:10.1016/j.neuron.2017.03.032 · Cited by 17 · see citing works
Cell-Type Specific Phase Precession in Layer II of the Medial Entorhinal Cortex
Reifenstein, E. T., Ebbesen, C. L., Tang, Q., Brecht, M., Schreiber, S., & Kempter, R. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.2986-15.2016 · Cited by 16 · see citing works
Gonzalez‐Sulser, A., & Nolan, M. F. (2016) · Nature Neuroscience · doi:10.1038/nn.4460 · Cited by 16 · see citing works
How does the modular organization of entorhinal grid cells develop?
Pilly, P. K., & Grossberg, S. (2014) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2014.00337 · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Perineuronal nets stabilize the grid cell network
Christensen, A. C., Lensjø, K. K., Lepperød, M. E., Dragly, S.-A., Sutterud, H., Blackstad, J. S., Fyhn, M., & Hafting, T. (2021) · Nature Communications · doi:10.1038/s41467-020-20241-w · Cited by 1,865 · see citing works
Kecskés, M., Henn-Mike, N., Agócs-Laboda, Á., Szőcs, S., Petykó, Z., & Varga, C. (2020) · Communications Biology · doi:10.1038/s42003-020-01496-x · Cited by 18 · see citing works
Place and behavioral modulation of hippocampal neurons during immobility
Sartorato, N., Zouridis, I. S., Narantsatsralt, U.-U., Blanco-Hernández, E., & Burgalossi, A. (2026) · Nature Communications · doi:10.1038/s41467-026-75492-w · Cited by 1 · see citing works
“6b and 3g) 135,136 .”
- Authors
- Zutshi, I., Fu, M. L., Lilascharoen, V., Leutgeb, J. K., Lim, B. K., & Leutgeb, S.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Leutgeb, Stefan
- Venue
- Nature Communications
- Published
- 2018-09-12
- Volume
- 9
- Issue
- 1
- Pages
- 3701-3701
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6135799
- OpenAlex
- W2892282934
- Cited by
- 57
- References
- 63
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 10 · 2023: 5 · 2022: 5 · 2021: 12 · 2020: 5 · 2019: 5
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Whitehall Foundation (20130571)
- National Institutes of Health
- National Institute of Mental Health (R01MH108594, R01MH100349, R01MH107742)
- National Institute of Neurological Disorders and Stroke (R01NS084324, R01NS086947, R01NS097772, R01NS102915)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Physical Sciences › Engineering › Automotive Engineering › Spatial Cognition and Navigation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- medial entorhinal cortex, grid cells, head direction cells, recurrent circuits, local circuits, product inhibition, optogenetic perturbation, spatial navigation, afferent input
- MeSH terms
- Grid Cells, Action Potentials, Animals, Female, Male, Pyramidal Cells, Entorhinal Cortex, Spatial Navigation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review