Intracellular Determinants of Hippocampal CA1 Place and Silent Cell Activity in a Novel Environment

For each environment a rodent has explored, its hippocampus contains a map consisting of a unique subset of neurons, called place cells, that have spatially tuned spiking there, with the remaining neurons being essentially silent. Using whole-cell recording in freely moving rats exploring a novel maze, we observed differences in intrinsic cellular properties and input-based subthreshold membrane potential levels underlying this division into place and silent cells. Compared to silent cells, place cells had lower spike thresholds and peaked versus flat subthreshold membrane potentials as a function of animal location. Both differences were evident from the beginning of exploration. Additionally, future place cells exhibited higher burst propensity before exploration. Thus, internal settings appear to predetermine which cells will represent the next novel environment encountered. Furthermore, place cells fired spatially tuned bursts with large, putatively calcium-mediated depolarizations that could trigger plasticity and stabilize the new map for long-term storage. Our results provide new insight into hippocampal memory formation.

[1]  A. J. Hill First occurrence of hippocampal spatial firing in a new environment , 1978, Experimental Neurology.

[2]  Dezhe Z. Jin,et al.  Support for a synaptic chain model of neuronal sequence generation , 2010, Nature.

[3]  G. Hu,et al.  Cholinergic Modulation of the Action Potential in Rat Hippocampal Neurons , 1996, The European journal of neuroscience.

[4]  D. D. Fraser,et al.  Cholinergic-Dependent Plateau Potential in Hippocampal CA1 Pyramidal Neurons , 1996, The Journal of Neuroscience.

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

[6]  R. Llinás,et al.  Hippocampal pyramidal cells: significance of dendritic ionic conductances for neuronal function and epileptogenesis. , 1979, Journal of neurophysiology.

[7]  Judit K. Makara,et al.  Compartmentalized dendritic plasticity and input feature storage in neurons , 2008, Nature.

[8]  Y. Yaari,et al.  Spike after‐depolarization and burst generation in adult rat hippocampal CA1 pyramidal cells. , 1996, The Journal of physiology.

[9]  Hiroyoshi Miyakawa,et al.  A plateau potential mediated by the activation of extrasynaptic NMDA receptors in rat hippocampal CA1 pyramidal neurons , 2008, The European journal of neuroscience.

[10]  C. Koch,et al.  Sparse Representation in the Human Medial Temporal Lobe , 2006, The Journal of Neuroscience.

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

[12]  L. Frank,et al.  Behavioral/Systems/Cognitive Hippocampal Plasticity across Multiple Days of Exposure to Novel Environments , 2022 .

[13]  M. Häusser,et al.  Encoding of Oscillations by Axonal Bursts in Inferior Olive Neurons , 2009, Neuron.

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

[15]  J. O’Keefe,et al.  Hippocampal place units in the freely moving rat: Why they fire where they fire , 1978, Experimental Brain Research.

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

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

[18]  K. I. Blum,et al.  Impaired Hippocampal Representation of Space in CA1-Specific NMDAR1 Knockout Mice , 1996, Cell.

[19]  C. Gray,et al.  Adaptive Coincidence Detection and Dynamic Gain Control in Visual Cortical Neurons In Vivo , 2003, Neuron.

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

[21]  P. Best,et al.  Place cells and silent cells in the hippocampus of freely-behaving rats , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

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

[23]  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.

[24]  D. Linden,et al.  The other side of the engram: experience-driven changes in neuronal intrinsic excitability , 2003, Nature Reviews Neuroscience.

[25]  G. Buzsáki,et al.  Temporal Interaction between Single Spikes and Complex Spike Bursts in Hippocampal Pyramidal Cells , 2001, Neuron.

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

[27]  R. Muller,et al.  The effects of changes in the environment on the spatial firing of hippocampal complex-spike cells , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[28]  Nathalie L Rochefort,et al.  Dendritic organization of sensory input to cortical neurons in vivo , 2010, Nature.

[29]  L. Nadel,et al.  The Hippocampus as a Cognitive Map , 1978 .

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

[31]  C. Koch,et al.  Invariant visual representation by single neurons in the human brain , 2005, Nature.

[32]  J. Magee,et al.  On the Initiation and Propagation of Dendritic Spikes in CA1 Pyramidal Neurons , 2004, The Journal of Neuroscience.

[33]  B. McNaughton,et al.  Independent Codes for Spatial and Episodic Memory in Hippocampal Neuronal Ensembles , 2005, Science.

[34]  Nelson Spruston,et al.  Plasticity of Burst Firing Induced by Synergistic Activation of Metabotropic Glutamate and Acetylcholine Receptors , 2009, Neuron.

[35]  Michael Brecht,et al.  Impact of Spikelets on Hippocampal CA1 Pyramidal Cell Activity During Spatial Exploration , 2010, Science.

[36]  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.

[37]  P. J. Sjöström,et al.  Spike timing, calcium signals and synaptic plasticity , 2002, Current Opinion in Neurobiology.

[38]  J. Lisman,et al.  The Input–Output Transformation of the Hippocampal Granule Cells: From Grid Cells to Place Fields , 2009, The Journal of Neuroscience.

[39]  Mattias P. Karlsson,et al.  Network Dynamics Underlying the Formation of Sparse, Informative Representations in the Hippocampus , 2008, The Journal of Neuroscience.

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

[41]  William W Lytton,et al.  Unmasking the CA1 Ensemble Place Code by Exposures to Small and Large Environments: More Place Cells and Multiple, Irregularly Arranged, and Expanded Place Fields in the Larger Space , 2008, The Journal of Neuroscience.

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

[43]  C Kentros,et al.  Abolition of long-term stability of new hippocampal place cell maps by NMDA receptor blockade. , 1998, Science.

[44]  Lucien T. Thompson,et al.  Long-term stability of the place-field activity of single units recorded from the dorsal hippocampus of freely behaving rats , 1990, Brain Research.

[45]  R. Passingham The hippocampus as a cognitive map J. O'Keefe & L. Nadel, Oxford University Press, Oxford (1978). 570 pp., £25.00 , 1979, Neuroscience.

[46]  P. Dudchenko The hippocampus as a cognitive map , 2010 .

[47]  G. Einevoll,et al.  From grid cells to place cells: A mathematical model , 2006, Hippocampus.

[48]  N Spruston,et al.  Resting and active properties of pyramidal neurons in subiculum and CA1 of rat hippocampus. , 2000, Journal of neurophysiology.

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

[50]  M. Quirk,et al.  Experience-Dependent Asymmetric Shape of Hippocampal Receptive Fields , 2000, Neuron.

[51]  A. Treves,et al.  Distinct Ensemble Codes in Hippocampal Areas CA3 and CA1 , 2004, Science.

[52]  J. Magee,et al.  Pathway Interactions and Synaptic Plasticity in the Dendritic Tuft Regions of CA1 Pyramidal Neurons , 2009, Neuron.

[53]  I. Fried,et al.  Internally Generated Reactivation of Single Neurons in Human Hippocampus During Free Recall , 2008, Science.

[54]  Matthew A. Wilson,et al.  Hippocampal Replay of Extended Experience , 2009, Neuron.

[55]  G. Dragoi,et al.  Preplay of future place cell sequences by hippocampal cellular assemblies , 2011, Nature.

[56]  Daniel Johnston,et al.  LTP is accompanied by an enhanced local excitability of pyramidal neuron dendrites , 2004, Nature Neuroscience.

[57]  Wendy W. Wu,et al.  Watermaze learning enhances excitability of CA1 pyramidal neurons. , 2003, Journal of neurophysiology.