Selection of distinct populations of dentate granule cells in response to inputs as a mechanism for pattern separation in mice

The hippocampus is critical for episodic memory and computational studies have predicted specific functions for each hippocampal subregion. Particularly, the dentate gyrus (DG) is hypothesized to perform pattern separation by forming distinct representations of similar inputs. How pattern separation is achieved by the DG remains largely unclear. By examining neuronal activities at a population level, we revealed that, unlike CA1 neuron populations, dentate granule cell (DGC) ensembles activated by learning were not preferentially reactivated by memory recall. Moreover, when mice encountered an environment to which they had not been previously exposed, a novel DGC population—rather than the previously activated DGC ensembles that responded to past events—was selected to represent the new environmental inputs. This selection of a novel responsive DGC population could be triggered by small changes in environmental inputs. Therefore, selecting distinct DGC populations to represent similar but not identical inputs is a mechanism for pattern separation. DOI: http://dx.doi.org/10.7554/eLife.00312.001

[1]  K. Deisseroth,et al.  Optogenetic stimulation of a hippocampal engram activates fear memory recall , 2012, Nature.

[2]  D Marr,et al.  Simple memory: a theory for archicortex. , 1971, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[3]  James L. McClelland,et al.  Hippocampal conjunctive encoding, storage, and recall: Avoiding a trade‐off , 1994, Hippocampus.

[4]  S. Tonegawa,et al.  Young Dentate Granule Cells Mediate Pattern Separation, whereas Old Granule Cells Facilitate Pattern Completion , 2012, Cell.

[5]  S. J. Martin,et al.  Reversible neural inactivation reveals hippocampal participation in several memory processes , 1999, Nature Neuroscience.

[6]  B L McNaughton,et al.  Hippocampal granule cells opt for early retirement , 2010, Hippocampus.

[7]  Michael R. Hunsaker,et al.  The interactions and dissociations of the dorsal hippocampus subregions: how the dentate gyrus, CA3, and CA1 process spatial information. , 2008, Behavioral neuroscience.

[8]  Lisa M. Saksida,et al.  Running enhances spatial pattern separation in mice , 2010, Proceedings of the National Academy of Sciences.

[9]  Paul E. Gilbert,et al.  Dissociating hippocampal subregions: A double dissociation between dentate gyrus and CA1 , 2001, Hippocampus.

[10]  E. Rolls,et al.  Computational analysis of the role of the hippocampus in memory , 1994, Hippocampus.

[11]  M. Fanselow Factors governing one-trial contextual conditioning , 1990 .

[12]  C. Houser Interneurons of the dentate gyrus: an overview of cell types, terminal fields and neurochemical identity. , 2007, Progress in brain research.

[13]  K. Deisseroth,et al.  Dynamics of Retrieval Strategies for Remote Memories , 2011, Cell.

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

[15]  E. Rolls,et al.  A computational theory of hippocampal function, and empirical tests of the theory , 2006, Progress in Neurobiology.

[16]  B. McNaughton,et al.  Mapping behaviorally relevant neural circuits with immediate-early gene expression , 2005, Current Opinion in Neurobiology.

[17]  R. McKay,et al.  Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus , 2001, The Journal of comparative neurology.

[18]  R. O’Reilly,et al.  Conjunctive representations, the hippocampus, and contextual fear conditioning , 2001, Cognitive, affective & behavioral neuroscience.

[19]  L. Saksida,et al.  A Functional Role for Adult Hippocampal Neurogenesis in Spatial Pattern Separation , 2009, Science.

[20]  Joshua P. Neunuebel,et al.  Spatial Firing Correlates of Physiologically Distinct Cell Types of the Rat Dentate Gyrus , 2012, The Journal of Neuroscience.

[21]  Alcino J. Silva,et al.  Molecular and Cellular Approaches to Memory Allocation in Neural Circuits , 2009, Science.

[22]  Gerd Kempermann,et al.  Experience-Induced Neurogenesis in the Senescent Dentate Gyrus , 1998, The Journal of Neuroscience.

[23]  M. Fanselow,et al.  NMDA receptor modulation of incidental learning in Pavlovian context conditioning. , 2004, Behavioral neuroscience.

[24]  F. Gage,et al.  Resolving New Memories: A Critical Look at the Dentate Gyrus, Adult Neurogenesis, and Pattern Separation , 2011, Neuron.

[25]  F. Gage,et al.  New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? , 2010, Nature Reviews Neuroscience.

[26]  J. Lassalle,et al.  Reversible Inactivation of the Hippocampal Mossy Fiber Synapses in Mice Impairs Spatial Learning, but neither Consolidation nor Memory Retrieval, in the Morris Navigation Task , 2000, Neurobiology of Learning and Memory.

[27]  R. O’Reilly,et al.  Hippocampal formation supports conditioning to memory of a context. , 2002, Behavioral neuroscience.

[28]  M. Wilson,et al.  Dentate Gyrus NMDA Receptors Mediate Rapid Pattern Separation in the Hippocampal Network , 2007, Science.

[29]  A. F. Schinder,et al.  A Distinctive layering pattern of mouse dentate granule cells is generated by developmental and adult neurogenesis , 2010, The Journal of comparative neurology.

[30]  M. Fanselow Contextual fear, gestalt memories, and the hippocampus , 2000, Behavioural Brain Research.

[31]  Bruno Bontempi,et al.  Selective Erasure of a Fear Memory , 2009, Science.

[32]  Gabriel M. Belfort,et al.  Npas4 Regulates a Transcriptional Program in CA3 Required for Contextual Memory Formation , 2011, Science.

[33]  M. Moser,et al.  Pattern Separation in the Dentate Gyrus and CA3 of the Hippocampus , 2007, Science.

[34]  Mark Mayford,et al.  Localization of a Stable Neural Correlate of Associative Memory , 2007, Science.

[35]  J. O’Neill,et al.  The reorganization and reactivation of hippocampal maps predict spatial memory performance , 2010, Nature Neuroscience.

[36]  E T Rolls,et al.  Computational constraints suggest the need for two distinct input systems to the hippocampal CA3 network , 1992, Hippocampus.

[37]  L. Squire Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. , 1992, Psychological review.

[38]  R. O’Reilly,et al.  Memory for context is impaired by injecting anisomycin into dorsal hippocampus following context exploration , 2002, Behavioural Brain Research.

[39]  Michael S. Fanselow,et al.  From contextual fear to a dynamic view of memory systems , 2010, Trends in Cognitive Sciences.

[40]  R. Kesner,et al.  Encoding versus retrieval of spatial memory: Double dissociation between the dentate gyrus and the perforant path inputs into CA3 in the dorsal hippocampus , 2004, Hippocampus.

[41]  E. Rolls A computational theory of episodic memory formation in the hippocampus , 2010, Behavioural Brain Research.

[42]  B. McNaughton,et al.  Sparse, environmentally selective expression of Arc RNA in the upper blade of the rodent fascia dentata by brief spatial experience , 2005, Hippocampus.