Intracellular dynamics of hippocampal place cells during virtual navigation

Hippocampal place cells encode spatial information in rate and temporal codes. To examine the mechanisms underlying hippocampal coding, here we measured the intracellular dynamics of place cells by combining in vivo whole-cell recordings with a virtual-reality system. Head-restrained mice, running on a spherical treadmill, interacted with a computer-generated visual environment to perform spatial behaviours. Robust place-cell activity was present during movement along a virtual linear track. From whole-cell recordings, we identified three subthreshold signatures of place fields: an asymmetric ramp-like depolarization of the baseline membrane potential, an increase in the amplitude of intracellular theta oscillations, and a phase precession of the intracellular theta oscillation relative to the extracellularly recorded theta rhythm. These intracellular dynamics underlie the primary features of place-cell rate and temporal codes. The virtual-reality system developed here will enable new experimental approaches to study the neural circuits underlying navigation.

[1]  E. Kandel,et al.  Electrophysiology of hippocampal neurons. II. After-potentials and repetitive firing. , 1961, Journal of neurophysiology.

[2]  E. Kandel,et al.  ELECTROPHYSIOLOGY OF HIPPOCAMPAL NEURONS: IV. FAST PREPOTENTIALS. , 1961, Journal of neurophysiology.

[3]  J. O'Keefe,et al.  The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. , 1971, Brain research.

[4]  J. B. Ranck,et al.  Studies on single neurons in dorsal hippocampal formation and septum in unrestrained rats. I. Behavioral correlates and firing repertoires. , 1973, Experimental neurology.

[5]  D. Prince,et al.  Participation of calcium spikes during intrinsic burst firing in hippocampal neurons , 1978, Brain Research.

[6]  G. Buzsáki,et al.  Cellular bases of hippocampal EEG in the behaving rat , 1983, Brain Research Reviews.

[7]  Paul S. Heckbert,et al.  Creating Raster Omnimax Images from Multiple Perspective Views Using the Elliptical Weighted Average Filter , 1986, IEEE Computer Graphics and Applications.

[8]  Ned Greene,et al.  Environment Mapping and Other Applications of World Projections , 1986, IEEE Computer Graphics and Applications.

[9]  P. Schwartzkroin,et al.  Electrophysiology of Hippocampal Neurons , 1987 .

[10]  G. H. Jacobs,et al.  Retinal receptors in rodents maximally sensitive to ultraviolet light , 1991, Nature.

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

[12]  B L McNaughton,et al.  Dynamics of the hippocampal ensemble code for space. , 1993, Science.

[13]  B. McNaughton,et al.  Population dynamics and theta rhythm phase precession of hippocampal place cell firing: A spiking neuron model , 1998, Hippocampus.

[14]  J. Lisman,et al.  Hippocampal CA3 region predicts memory sequences: accounting for the phase precession of place cells. , 1996, Learning & memory.

[15]  B. McNaughton,et al.  Theta phase precession in hippocampal neuronal populations and the compression of temporal sequences , 1996, Hippocampus.

[16]  M. Hasselmo,et al.  GABAergic modulation of hippocampal population activity: sequence learning, place field development, and the phase precession effect. , 1997, Journal of neurophysiology.

[17]  M. Srinivasan,et al.  Reflective surfaces for panoramic imaging. , 1997, Applied optics.

[18]  G. Buzsáki,et al.  Theta oscillations in somata and dendrites of hippocampal pyramidal cells in vivo: Activity‐dependent phase‐precession of action potentials , 1998, Hippocampus.

[19]  Bruce L. McNaughton,et al.  Environment-specific expression of the immediate-early gene Arc in hippocampal neuronal ensembles , 1999, Nature Neuroscience.

[20]  M. Quirk,et al.  Interaction between spike waveform classification and temporal sequence detection , 1999, Journal of Neuroscience Methods.

[21]  J. Csicsvari,et al.  Intracellular features predicted by extracellular recordings in the hippocampus in vivo. , 2000, Journal of neurophysiology.

[22]  J. Magee Dendritic mechanisms of phase precession in hippocampal CA1 pyramidal neurons. , 2001, Journal of neurophysiology.

[23]  G. Buzsáki,et al.  Spike train dynamics predicts theta-related phase precession in hippocampal pyramidal cells , 2002, Nature.

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

[25]  G. Buzsáki Theta Oscillations in the Hippocampus , 2002, Neuron.

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

[27]  M. Quirk,et al.  Hippocampal CA3 NMDA Receptors Are Crucial for Memory Acquisition of One-Time Experience , 2003, Neuron.

[28]  M. Lengyel,et al.  Dynamically detuned oscillations account for the coupled rate and temporal code of place cell firing , 2003, Hippocampus.

[29]  Linus Da-Shih Sun Impaired and enhanced spatial representation of the PSD-95 knockout mouse , 2003 .

[30]  B. McNaughton,et al.  The contributions of position, direction, and velocity to single unit activity in the hippocampus of freely-moving rats , 1983, Experimental Brain Research.

[31]  E. Kandel,et al.  Increased Attention to Spatial Context Increases Both Place Field Stability and Spatial Memory , 2004, Neuron.

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

[33]  J. O’Keefe,et al.  Dual phase and rate coding in hippocampal place cells: Theoretical significance and relationship to entorhinal grid cells , 2005, Hippocampus.

[34]  Albert K. Lee,et al.  Whole-Cell Recordings in Freely Moving Rats , 2006, Neuron.

[35]  R. E. Brown,et al.  Visual detection, pattern discrimination and visual acuity in 14 strains of mice , 2006, Genes, brain, and behavior.

[36]  Alan Gelperin,et al.  Sparse Odor Coding in Awake Behaving Mice , 2006, The Journal of Neuroscience.

[37]  J. Magee,et al.  State-Dependent Dendritic Computation in Hippocampal CA1 Pyramidal Neurons , 2006, The Journal of Neuroscience.

[38]  C. Petersen,et al.  Correlating whisker behavior with membrane potential in barrel cortex of awake mice , 2006, Nature Neuroscience.

[39]  Karl Peter Giese,et al.  Experience-Dependent Increase in CA1 Place Cell Spatial Information, But Not Spatial Reproducibility, Is Dependent on the Autophosphorylation of the α-Isoform of the Calcium/Calmodulin-Dependent Protein Kinase II , 2007, The Journal of Neuroscience.

[40]  B. McNaughton,et al.  Network and intrinsic cellular mechanisms underlying theta phase precession of hippocampal neurons , 2007, Trends in Neurosciences.

[41]  D. Tank,et al.  Imaging Large-Scale Neural Activity with Cellular Resolution in Awake, Mobile Mice , 2007, Neuron.

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

[43]  K. Svoboda,et al.  Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice , 2008, Nature.

[44]  Emilio Kropff,et al.  Place cells, grid cells, and the brain's spatial representation system. , 2008, Annual review of neuroscience.

[45]  Michael Brecht,et al.  Head-anchored whole-cell recordings in freely moving rats , 2009, Nature Protocols.