Cellular mechanisms of spatial navigation in the medial entorhinal cortex

Neurons in the medial entorhinal cortex exhibit a grid-like spatial pattern of spike rates that has been proposed to represent a neural code for path integration. To understand how grid cell firing arises from the combination of intrinsic conductances and synaptic input in medial entorhinal stellate cells, we performed patch-clamp recordings in mice navigating in a virtual-reality environment. We found that the membrane potential signature of stellate cells during firing field crossings consisted of a slow depolarization driving spike output. This was best predicted by network models in which neurons receive sustained depolarizing synaptic input during a field crossing, such as continuous attractor network models of grid cell firing. Another key feature of the data, phase precession of intracellular theta oscillations and spiking with respect to extracellular theta oscillations, was best captured by an oscillatory interference model. Thus, these findings provide crucial new information for a quantitative understanding of the cellular basis of spatial navigation in the entorhinal cortex.

[1]  N. Mangini,et al.  Retinotopic organization of striate and extrastriate visual cortex in the mouse , 1980, The Journal of comparative neurology.

[2]  J. O’Keefe,et al.  Phase relationship between hippocampal place units and the EEG theta rhythm , 1993, Hippocampus.

[3]  A. Alonso,et al.  Differential electroresponsiveness of stellate and pyramidal-like cells of medial entorhinal cortex layer II. , 1993, Journal of neurophysiology.

[4]  A. Alonso,et al.  Morphological characteristics of layer II projection neurons in the rat medial entorhinal cortex , 1997, Hippocampus.

[5]  B. Sakmann,et al.  In vivo, low-resistance, whole-cell recordings from neurons in the anaesthetized and awake mammalian brain , 2002, Pflügers Archiv.

[6]  J. White,et al.  Frequency selectivity of layer II stellate cells in the medial entorhinal cortex. , 2002, Journal of neurophysiology.

[7]  M. R. Mehta,et al.  Role of experience and oscillations in transforming a rate code into a temporal code , 2002, Nature.

[8]  Michael E Hasselmo,et al.  Ionic mechanisms in the generation of subthreshold oscillations and action potential clustering in entorhinal layer II stellate neurons , 2004, Hippocampus.

[9]  Paul D. Bourke.  Spherical mirror: a new approach to hemispherical dome projection , 2005, GRAPHITE '05.

[10]  A Schnee,et al.  Rats are able to navigate in virtual environments , 2005, Journal of Experimental Biology.

[11]  T. Hafting,et al.  Microstructure of a spatial map in the entorhinal cortex , 2005, Nature.

[12]  Michael L. Hines,et al.  The NEURON Book , 2006 .

[13]  Bruce L. McNaughton,et al.  Path integration and the neural basis of the 'cognitive map' , 2006, Nature Reviews Neuroscience.

[14]  Jonathan D. Cohen,et al.  Conjunctive Representation of Position, Direction, and Velocity in Entorhinal Cortex , 2006 .

[15]  Mark C. Fuhs,et al.  A Spin Glass Model of Path Integration in Rat Medial Entorhinal Cortex , 2006, The Journal of Neuroscience.

[16]  J. O’Keefe,et al.  An oscillatory interference model of grid cell firing , 2007, Hippocampus.

[17]  Lisa M. Giocomo,et al.  Grid cell firing may arise from interference of theta frequency membrane potential oscillations in single neurons , 2007, Hippocampus.

[18]  Lisa M. Giocomo,et al.  Temporal Frequency of Subthreshold Oscillations Scales with Entorhinal Grid Cell Field Spacing , 2007, Science.

[19]  M. Nolan,et al.  HCN1 Channels Control Resting and Active Integrative Properties of Stellate Cells from Layer II of the Entorhinal Cortex , 2007, The Journal of Neuroscience.

[20]  Alessandro Treves,et al.  The emergence of grid cells: Intelligent design or just adaptation? , 2008, Hippocampus.

[21]  M. Fyhn,et al.  Progressive increase in grid scale from dorsal to ventral medial entorhinal cortex , 2008, Hippocampus.

[22]  T. Hafting,et al.  Hippocampus-independent phase precession in entorhinal grid cells , 2008, Nature.

[23]  T. Hafting,et al.  Grid cells in mice , 2008, Hippocampus.

[24]  John A White,et al.  Artificial Synaptic Conductances Reduce Subthreshold Oscillations and Periodic Firing in Stellate Cells of the Entorhinal Cortex , 2008, The Journal of Neuroscience.

[25]  M. Nolan,et al.  Tuning of Synaptic Integration in the Medial Entorhinal Cortex to the Organization of Grid Cell Firing Fields , 2008, Neuron.

[26]  N. Burgess.  Grid cells and theta as oscillatory interference: Theory and predictions , 2008, Hippocampus.

[27]  N. Spruston,et al.  Synapse Distribution Suggests a Two-Stage Model of Dendritic Integration in CA1 Pyramidal Neurons , 2009, Neuron.

[28]  D. Tank,et al.  Intracellular dynamics of hippocampal place cells during virtual navigation , 2009, Nature.

[29]  Yoram Burakyy,et al.  Accurate Path Integration in Continuous Attractor Network Models of Grid Cells , 2009 .

[30]  M. Hasselmo,et al.  Coupled Noisy Spiking Neurons as Velocity-Controlled Oscillators in a Model of Grid Cell Spatial Firing , 2010, The Journal of Neuroscience.

[31]  G. Buzsáki,et al.  Intrinsic Circuit Organization and Theta–Gamma Oscillation Dynamics in the Entorhinal Cortex of the Rat , 2010, The Journal of Neuroscience.

[32]  Ashley N. Linder,et al.  The Spatial Periodicity of Grid Cells Is Not Sustained During Reduced Theta Oscillations , 2011, Science.

[33]  Matthew F Nolan,et al.  Dorsal–ventral organization of theta‐like activity intrinsic to entorhinal stellate neurons is mediated by differences in stochastic current fluctuations , 2011, The Journal of physiology.

[34]  Mark P. Brandon,et al.  Reduction of Theta Rhythm Dissociates Grid Cell Spatial Periodicity from Directional Tuning , 2011, Science.

[35]  M. Yartsev,et al.  Grid cells without theta oscillations in the entorhinal cortex of bats , 2011, Nature.

[36]  Neil Burgess,et al.  Models of place and grid cell firing and theta rhythmicity , 2011, Current Opinion in Neurobiology.

[37]  H. T. Blair,et al.  Cosine Directional Tuning of Theta Cell Burst Frequencies: Evidence for Spatial Coding by Oscillatory Interference , 2011, The Journal of Neuroscience.

[38]  R. Kempter,et al.  Grid cells in rat entorhinal cortex encode physical space with independent firing fields and phase precession at the single-trial level , 2012, Proceedings of the National Academy of Sciences.

[39]  Richard Kempter,et al.  Quantifying circular–linear associations: Hippocampal phase precession , 2012, Journal of Neuroscience Methods.

[40]  Lisa M. Giocomo,et al.  Phase precession and variable spatial scaling in a periodic attractor map model of medial entorhinal grid cells with realistic after‐spike dynamics , 2012, Hippocampus.

[41]  Lisa M. Giocomo,et al.  Neural Circuits Original Research Article a Model Combining Oscillations and Attractor Dynamics for Generation of Grid Cell Firing , 2012 .

[42]  Eric A. Zilli,et al.  Models of Grid Cell Spatial Firing Published 2005–2011 , 2012, Front. Neural Circuits.

[43]  Benjamin A. Dunn,et al.  Recurrent inhibitory circuitry as a mechanism for grid formation , 2013, Nature Neuroscience.

[44]  M. V. Rossum,et al.  Feedback Inhibition Enables Theta-Nested Gamma Oscillations and Grid Firing Fields , 2013, Neuron.