title: The CRISP theory of hippocampal function in episodic memory.
abstract: Over the past four decades, a "standard framework" has emerged to explain the neural mechanisms of episodic memory storage. This framework has been instrumental in driving hippocampal research forward and now dominates the design and interpretation of experimental and theoretical studies. It postulates that cortical inputs drive plasticity in the recurrent cornu ammonis 3 (CA3) synapses to rapidly imprint memories as attractor states in CA3. Here we review a range of experimental studies and argue that the evidence against the standard framework is mounting, notwithstanding the considerable evidence in its support. We propose CRISP as an alternative theory to the standard framework. CRISP is based on Context Reset by dentate gyrus (DG), Intrinsic Sequences in CA3, and Pattern completion in cornu ammonis 1 (CA1). Compared to previous models, CRISP uses a radically different mechanism for storing episodic memories in the hippocampus. Neural sequences are intrinsic to CA3, and inputs are mapped onto these intrinsic sequences through synaptic plasticity in the feedforward projections of the hippocampus. Hence, CRISP does not require plasticity in the recurrent CA3 synapses during the storage process. Like in other theories DG and CA1 play supporting roles, however, their function in CRISP have distinct implications. For instance, CA1 performs pattern completion in the absence of CA3 and DG contributes to episodic memory retrieval, increasing the speed, precision, and robustness of retrieval. We propose the conceptual theory, discuss its implications for experimental results and suggest testable predictions. It appears that CRISP not only accounts for those experimental results that are consistent with the standard framework, but also for results that are at odds with the standard framework. We therefore suggest that CRISP is a viable, and perhaps superior, theory for the hippocampal function in episodic memory.
authors: Mercator Research Group "Structure of Memory", Ruhr-Universität Bochum Bochum, Germany ; Faculty of Psychology, Ruhr-Universität Bochum Bochum, Germany.
authors: Sen
authors: S
authors: Cheng
mesh_terms: D000818:Animals; D018891:Dentate Gyrus / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology; D006801:Humans; D061212:Memory, Episodic; D008959:Models, Neurological; D009473:Neuronal Plasticity / Q000502:physiology*
keywords: CA1; CA3; dentate gyrus; episodic memory; hippocampus; pattern completion; pattern separation; standard model
references: Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2367-72
references: 20133882
references: Hippocampus. 1996;6(6):579-90
references: 9034847
references: Ann N Y Acad Sci. 1985;444:533-5
references: 3860120
references: J Neurophysiol. 2002 Feb;87(2):669-78
references: 11826036
references: Nat Neurosci. 2004 Mar;7(3):286-94
references: 14983183
references: Hippocampus. 1996;6(6):654-65
references: 9034852
references: Nature. 2004 May 13;429(6988):184-7
references: 15107864
references: Hippocampus. 1994 Jun;4(3):374-91
references: 7842058
references: Nature. 2011 Sep 28;478(7368):246-9
references: 21964339
references: J Neurosci. 1997 Aug 1;17(15):5900-20
references: 9221787
references: Trends Neurosci. 1998 Aug;21(8):317-23
references: 9720595
references: Science. 2008 Sep 5;321(5894):1322-7
references: 18772431
references: J Neurosci. 2009 Jan 28;29(4):898-906
references: 19176799
references: Hippocampus. 1992 Apr;2(2):189-99
references: 1308182
references: Psychol Rev. 1995 Jul;102(3):419-457
references: 7624455
references: J Neurosci. 2006 Feb 1;26(5):1562-70
references: 16452679
references: Neural Plast. 2007;2007:90472
references: 18274617
references: Nat Neurosci. 2002 Aug;5(8):790-5
references: 12118256
references: Hippocampus. 2012 Feb;22(2):292-8
references: 21049483
references: Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):E718-24
references: 21844350
references: Psychol Rev. 2007 Apr;114(2):340-75
references: 17500630
references: Neuron. 2002 Dec 19;36(6):1183-94
references: 12495631
references: Neuron. 2002 Oct 24;36(3):527-38
references: 12408854
references: Science. 1990 Oct 12;250(4978):288-90
references: 2218534
references: Neuron. 2003 Apr 24;38(2):305-15
references: 12718863
references: Hippocampus. 2001;11(5):578-98
references: 11732710
references: Hippocampus. 1999;9(2):118-36
references: 10226773
references: Science. 2011 Dec 9;334(6061):1415-20
references: 22052975
references: Hippocampus. 1996;6(6):693-708
references: 9034856
references: J Neurosci. 2004 Jul 21;24(29):6489-96
references: 15269259
references: Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1726-31
references: 17229836
references: Nature. 1982 Jun 24;297(5868):681-3
references: 7088155
references: Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):19044-8
references: 20956323
references: Science. 1992 May 1;256(5057):675-7
references: 1585183
references: Nat Neurosci. 2002 May;5(5):458-62
references: 11976705
references: Nature. 2006 Mar 30;440(7084):680-3
references: 16474382
references: Hippocampus. 2001;11(4):408-17
references: 11530845
references: Neuron. 1999 Feb;22(2):233-42
references: 10069330
references: Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13858-63
references: 21810986
references: J Neurosci. 2008 Dec 24;28(52):14271-81
references: 19109508
references: Nature. 2005 Aug 11;436(7052):801-6
references: 15965463
references: Nature. 2003 Jul 10;424(6945):205-9
references: 12853960
references: J Neurosci. 2009 Mar 18;29(11):3475-84
references: 19295153
references: Science. 2005 May 6;308(5723):873-6
references: 15879220
references: J Neurosci. 1998 Jan 15;18(2):804-10
references: 9425021
references: Science. 1968 May 3;160(3827):554-5
references: 5689415
references: Science. 2004 Aug 27;305(5688):1295-8
references: 15272123
references: Nature. 1996 May 30;381(6581):425-8
references: 8632799
references: Neuropsychologia. 2008 Mar 7;46(4):1050-9
references: 18155255
references: Science. 2002 Jun 21;296(5576):2243-6
references: 12077421
references: Hippocampus. 2004;14(2):148-52
references: 15098720
references: Nature. 2005 Mar 31;434(7033):567
references: 15800602
references: Philos Trans R Soc Lond B Biol Sci. 1971 Jul 1;262(841):23-81
references: 4399412
references: Science. 2007 Jul 6;317(5834):94-9
references: 17556551
references: Neuroscience. 2011 Dec 1;197:293-306
references: 21963867
references: Nature. 2004 Sep 23;431(7007):453-6
references: 15386013
references: Neural Comput. 1998 Jan 1;10(1):25-57
references: 9501503
references: PLoS One. 2012;7(8):e43495
references: 22937055
references: J Neurophysiol. 2001 Jun;85(6):2423-31
references: 11387388
references: J Neurophysiol. 2010 Jul;104(1):35-50
references: 20445029
references: PLoS One. 2012;7(4):e36035
references: 22558316
references: Neuropsychologia. 2010 Sep;48(11):3187-92
references: 20603137
references: Neuron. 2008 Jan 24;57(2):303-13
references: 18215626
references: Neuron. 2002 Aug 15;35(4):625-41
references: 12194864
references: Nature. 2004 Oct 7;431(7009):699-703
references: 15470431
references: Hippocampus. 2005;15(6):722-38
references: 15986407
references: Neural Plast. 2011;2011:203462
references: 21918724
references: Science. 2002 Jul 12;297(5579):211-8
references: 12040087
references: J Neurosci. 2004 Sep 1;24(35):7681-9
references: 15342735
references: Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17169-73
references: 17940008
references: Neuroscience. 2008 Jul 17;154(4):1155-72
references: 18554812
references: Science. 1985 May 3;228(4699):604-6
references: 3983648
references: Neural Comput. 2002 Apr;14(4):715-70
references: 11936959
references: Hippocampus. 2010 Jan;20(1):11-8
references: 19405148
references: J Neurosci. 1996 Mar 15;16(6):2027-33
references: 8604047
references: Nat Neurosci. 2010 Aug;13(8):995-1002
references: 20639874
references: Neuron. 2009 Jun 25;62(6):781-7
references: 19555647
references: J Cogn Neurosci. 1991 Spring;3(2):190-202
references: 23972093
references: PLoS One. 2007 May 23;2(5):e455
references: 17520014
references: Nature. 2011 Jan 20;469(7330):397-401
references: 21179088
references: Brain Res. 1971 Nov;34(1):171-5
references: 5124915
references: Hippocampus. 2006;16(4):379-87
references: 16411184
references: Behav Brain Res. 1990 May 7;38(2):145-54
references: 2363834
references: Science. 2008 Feb 29;319(5867):1260-4
references: 18218862
references: Neuron. 2004 Jun 10;42(5):803-15
references: 15182719
references: Neuroscience. 1989;31(3):551-70
references: 2687720
references: Nature. 2002 Apr 18;416(6882):736-40
references: 11961555
references: Hippocampus. 2001;11(5):551-68
references: 11732708
references: Science. 2008 Jul 4;321(5885):140-3
references: 18599792
references: Brain. 2008 Jul;131(Pt 7):1806-17
references: 18503077
references: Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5263-7
references: 10220454
references: PLoS One. 2010 Jan 29;5(1):e8809
references: 20126454
references: Psychol Rev. 1979 Jan;86(1):44-60
references: 451113
references: Neuroscience. 2010 Sep 29;170(1):156-65
references: 20600643
references: Neuron. 2009 Jul 30;63(2):267-76
references: 19640484
references: Nat Neurosci. 2008 Feb;11(2):209-15
references: 18193040
references: Proc Natl Acad Sci U S A. 1982 Apr;79(8):2554-8
references: 6953413
references: Nature. 1969 Jun 7;222(5197):960-2
references: 5789326
references: Neurobiol Learn Mem. 2000 May;73(3):243-57
references: 10775494
references: Hippocampus. 1994 Dec;4(6):661-82
references: 7704110
references: Hippocampus. 2005;15(6):808-14
references: 16010664
references: Proc Natl Acad Sci U S A. 2011 Jan 18;108(3):1146-51
references: 21199935
references: Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):7109-14
references: 9192700
references: Nature. 2002 Mar 7;416(6876):90-4
references: 11882899
references: Hippocampus. 2008;18(7):710-8
references: 18446823
references: Neuropsychologia. 2005;43(4):609-24
references: 15716151
references: Nature. 2002 Feb 28;415(6875):1030-4
references: 11875571
references: Science. 2012 Jun 15;336(6087):1454-8
references: 22555434
references: Hippocampus. 2010 Jan;20(1):24-8
references: 19499585
references: Neuropsychologia. 2005;43(4):479-96
references: 15716139
references: Learn Mem. 2009 May 23;16(6):387-94
references: 19470655
references: Behav Neurosci. 1986 Apr;100(2):147-54
references: 3008780
references: Hippocampus. 2004;14(8):1000-10
references: 15390172
references: Science. 2007 Aug 17;317(5840):951-3
references: 17702943
references: Neuroreport. 1995 Dec 15;6(18):2479-82
references: 8741746
references: J Neurol Neurosurg Psychiatry. 1957 Feb;20(1):11-21
references: 13406589
references: Neurobiol Learn Mem. 2005 Jan;83(1):65-71
references: 15607690
references: Behav Brain Res. 1999 Mar;99(2):123-32
references: 10512579
references: Neuron. 2005 Oct 20;48(2):345-58
references: 16242413
references: Hippocampus. 1998;8(6):638-46
references: 9882021
references: Hippocampus. 2006;16(3):216-24
references: 16421862
references: Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3194-8
references: 11867718
references: Neuron. 2004 Nov 18;44(4):581-4
references: 15541306
references: Neuron. 2010 Mar 11;65(5):695-705
references: 20223204
references: Science. 1993 Aug 20;261(5124):1055-8
references: 8351520
references: Nature. 2004 Jul 22;430(6998):456-9
references: 15229614
references: Hippocampus. 2004;14(2):153-62
references: 15098721
references: Nat Neurosci. 2009 Oct;12(10):1222-3
references: 19749750
references: Neuron. 1999 Jun;23(2):209-26
references: 10399928
references: Science. 2004 Apr 2;304(5667):78-80
references: 15064413
references: Science. 2009 Jul 10;325(5937):210-3
references: 19590004
references: Nat Neurosci. 2007 Oct;10(10):1241-2
references: 17828259
references: Trends Cogn Sci. 1999 Sep;3(9):351-359
references: 10461198
references: Curr Opin Neurobiol. 1997 Apr;7(2):217-27
references: 9142752
references: Eur J Neurosci. 2007 Aug;26(3):704-16
references: 17651429
references: Hippocampus. 2001;11(6):626-36
references: 11811656
references: Nature. 1996 Jan 18;379(6562):255-7
references: 8538790
references: Hippocampus. 2004;14(1):66-76
references: 15058484
references: Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7041-5
references: 8041742
references: Neuron. 2011 Aug 25;71(4):737-49
references: 21867888
references: Neuron. 2009 Jan 29;61(2):187-202
references: 19186162
references: J Neurosci. 1995 Jan;15(1 Pt 1):30-46
references: 7823136
references: Q J Exp Psychol B. 1994 May;47(2):129-50
references: 8052726
references: Science. 2011 Aug 5;333(6043):773-6
references: 21817056
references: Neural Comput. 2002 Apr;14(4):793-817
references: 11936962
references: Hippocampus. 1993 Oct;3(4):491-516
references: 8269040
references: J Neurosci. 2011 Feb 23;31(8):2828-34
references: 21414904
references: Neuropsychologia. 2006;44(3):489-506
references: 16023686
references: Nature. 2011 Apr 28;472(7344):466-70
references: 21460835
references: Eur J Neurosci. 2006 Sep;24(6):1771-80
references: 17004940
references: J Neurophysiol. 2004 Feb;91(2):863-72
references: 14523073
references: Science. 2007 Feb 16;315(5814):961-6
references: 17303747
references: Hippocampus. 2000;10(4):352-68
references: 10985275
references: Science. 1997 Jul 18;277(5324):376-80
references: 9219696
references: Hippocampus. 2006;16(3):329-43
references: 16435309
references: Science. 2008 Mar 21;319(5870):1640-2
references: 18356518
references: Cell. 2012 Mar 30;149(1):188-201
references: 22365813