title: Selection of distinct populations of dentate granule cells in response to inputs as a mechanism for pattern separation in mice.
abstract: 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.
authors.affiliation: Laboratory of Genetics , The Salk Institute for Biological Studies , La Jolla , United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Mark
authors.initials: M
authors.lastname: Mayford
authors.forename: Fred H
authors.initials: FH
authors.lastname: Gage
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001931:Brain Mapping; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D003213:Conditioning, Psychological; D003463:Cues; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D004777:Environment; D005239:Fear; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D008568:Memory; D061212:Memory, Episodic; D011939:Mental Recall; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D046709:Pattern Recognition, Physiological; D013997:Time Factors
keywords: CA1; Mouse; dentate gyrus; hippocampus; learning and memory; pattern separation
references.citation: Hippocampus. 2005;15(5):579-86
references.pmid: 15920719
references.citation: Trends Cogn Sci. 2010 Jan;14(1):7-15
references.pmid: 19939724
references.citation: Behav Brain Res. 2010 Dec 31;215(2):180-96
references.pmid: 20307583
references.citation: J Neurosci. 2012 Mar 14;32(11):3848-58
references.pmid: 22423105
references.citation: Science. 2004 Aug 27;305(5688):1295-8
references.pmid: 15272123
references.citation: Neuron. 2011 May 26;70(4):589-96
references.pmid: 21609818
references.citation: Nature. 2012 Mar 22;484(7394):381-5
references.pmid: 22441246
references.citation: Curr Opin Neurobiol. 2005 Oct;15(5):599-606
references.pmid: 16150584
references.citation: Nat Neurosci. 2010 Aug;13(8):995-1002
references.pmid: 20639874
references.citation: Nat Neurosci. 1999 Oct;2(10):898-905
references.pmid: 10491611
references.citation: J Neurosci. 1998 May 1;18(9):3206-12
references.pmid: 9547229
references.citation: Hippocampus. 2001;11(6):626-36
references.pmid: 11811656
references.citation: Hippocampus. 2004;14(1):66-76
references.pmid: 15058484
references.citation: Prog Brain Res. 2007;163:217-32
references.pmid: 17765721
references.citation: Cogn Affect Behav Neurosci. 2001 Mar;1(1):66-82
references.pmid: 12467104
references.citation: Science. 2009 Mar 13;323(5920):1492-6
references.pmid: 19286560
references.citation: Hippocampus. 1994 Jun;4(3):374-91
references.pmid: 7842058
references.citation: Behav Neurosci. 2004 Feb;118(1):253-7
references.pmid: 14979804
references.citation: Behav Neurosci. 2002 Aug;116(4):530-8
references.pmid: 12148921
references.citation: Nat Rev Neurosci. 2010 May;11(5):339-50
references.pmid: 20354534
references.citation: Behav Brain Res. 2000 Jun 1;110(1-2):73-81
references.pmid: 10802305
references.citation: Hippocampus. 1992 Apr;2(2):189-99
references.pmid: 1308182
references.citation: Cell. 2011 Oct 28;147(3):678-89
references.pmid: 22019004
references.citation: Hippocampus. 2010 Oct;20(10):1109-23
references.pmid: 20872737
references.citation: Behav Brain Res. 2002 Aug 21;134(1-2):299-306
references.pmid: 12191817
references.citation: Behav Neurosci. 2008 Feb;122(1):16-26
references.pmid: 18298245
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2367-72
references.pmid: 20133882
references.citation: Philos Trans R Soc Lond B Biol Sci. 1971 Jul 1;262(841):23-81
references.pmid: 4399412
references.citation: Science. 2007 Jul 6;317(5834):94-9
references.pmid: 17556551
references.citation: Science. 2009 Oct 16;326(5951):391-5
references.pmid: 19833959
references.citation: Science. 2007 Aug 31;317(5842):1230-3
references.pmid: 17761885
references.citation: Neurobiol Learn Mem. 2000 May;73(3):243-57
references.pmid: 10775494
references.citation: Hippocampus. 1994 Dec;4(6):661-82
references.pmid: 7704110
references.citation: Psychol Rev. 1992 Apr;99(2):195-231
references.pmid: 1594723
references.citation: Prog Neurobiol. 2006 May;79(1):1-48
references.pmid: 16781044
references.citation: J Comp Neurol. 2010 Nov 15;518(22):4479-90
references.pmid: 20886617
references.citation: J Comp Neurol. 2001 Jul 9;435(4):406-17
references.pmid: 11406822
references.citation: Science. 2011 Dec 23;334(6063):1669-75
references.pmid: 22194569
references.citation: Science. 2009 Jul 10;325(5937):210-3
references.pmid: 19590004
references.citation: Science. 2007 Feb 16;315(5814):961-6
references.pmid: 17303747
references.citation: Cell. 2012 Mar 30;149(1):188-201
references.pmid: 22365813