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Frontiers in Biology

Front. Biol.    2016, Vol. 11 Issue (3) : 168-181     DOI: 10.1007/s11515-016-1406-2
REVIEW |
Adult neurogenesis and pattern separation in rodents: A critical evaluation of data, tasks and interpretation
Martha Hvoslef-Eide1,2,3,Charlotte A. Oomen4,5,6,*()
1. Department of Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom
2. Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3 EB, United Kingdom
3. Current addess Department of Biosciences, University of Oslo, 0370 Oslo, Norway
4. Department of Cognitive Neuroscience, Radboud University Medical Center, Donders Institute, Geert Grooteplein 21, 6500 HB, Nijmegen, The Netherlands
5. Current address Centre for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands
6. Current address Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands
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Abstract

The ability to discriminate and store similar inputs as distinct representations in memory is thought to rely on a process called pattern separation in the dentate gyrus of the hippocampus. Recent computational and empirical findings support a role for adult-born granule neurons in spatial pattern separation. We reviewed rodent studies that have manipulated both hippocampal adult neurogenesis and assessed pattern separation. The majority of studies report a supporting role of adult born neurons in pattern separation as measured at the behavioral level. However, closer evaluation of the published findings reveals variation in both pattern separation tasks and in the interpretation of behavioral performance that, taken together, suggests that the role of hippocampal adult neurogenesis in pattern separation may be less established than is currently assumed. Assessment of pattern separation at the network level through the use of immediate early gene expression, optogenetic, pharmacogenetic and/or in vivo electrophysiology studies could be instrumental in further confirming a role of adult born neurons in pattern separation further. Finally, hippocampal adult neurogenesis and pattern separation are not an exclusive pair, as evidence for hippocampal adult neurogenesis contributing to the temporal separation of events in memory, forgetting and cognitive flexibility has also been found. We conclude that whereas current empirical evidence for the involvement of hippocampal adult neurogenesis in pattern separation seems supportive, there is a need for careful interpretation of behavioral findings and an integration of the various proposed functions of adult born neurons.

Keywords adult neurogenesis      memory      pattern separation      dentate gyrus      behavioral paradigms     
Corresponding Authors: Charlotte A. Oomen   
Just Accepted Date: 01 June 2016   Online First Date: 23 June 2016    Issue Date: 05 July 2016
 Cite this article:   
Martha Hvoslef-Eide,Charlotte A. Oomen. Adult neurogenesis and pattern separation in rodents: A critical evaluation of data, tasks and interpretation[J]. Front. Biol., 2016, 11(3): 168-181.
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http://journal.hep.com.cn/fib/EN/10.1007/s11515-016-1406-2
http://journal.hep.com.cn/fib/EN/Y2016/V11/I3/168
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Martha Hvoslef-Eide
Charlotte A. Oomen
Effect on task(s) Dissimilar condition? Support role of NG in PS? Change in NG/experimental manipulation Species/Sex/Age Reference
1 Impaired novel object in place recognition memory No Yes Decreased NG after early malnutrition Rat/m/- Perez-Garcia et al., 2016
2 No effect on location discrimination learning (touchscreen) Yes No Increased NG after electroconvulsive seazures Rat/m/8+ weeks Svensson et al., 2016
3 Improved performance on the DNMTP radial arm maze Yes Yes Innate higher levels of NG correlate positively with task performance in male spatial strategy users. Rat/m and f/10+ weeks Yagi et al., 2016
4 Improved performance on contextual fear discrimination (in 3 month old mice) No Yes Increased NG after fingolimod treatment Mice/m/ 3,7,12 months Efstathopoulos et al., 2015
5 No effect on contextual fear discrimination No No Decreased NG in a Dorfin homozygous knockout mouse Mice/-/- Park et al., 2015
6 No effect on trial-unique nonmatching to location (touchscreen) Yes No Increased neurogenesis after electroconvulsive seazures Rat/m/8+weeks Svensson et al., 2015
7 Improved contextual fear discrimination No Yes Increased NG after postnatal sevoflurane treatment Rat/m/5–8 weeks Chen et al., 2015
8 Impaired learning in a high-interference condition of submerged T-maze paradigm Yes, low interference Yes Decreased NG after chemotherapy drug treatment Rat/f/5 months Winocur et al., 2015
9 Improved contextual fear discrimination after running in aged animals No Yes Decreased NG in aging, increased neurogenesis after voluntary exercise Mice/m/2,17 months Wu et al., 2015
10 Improved novel object recognition of similar, but not distinct objects Yes Yes Increased NG after voluntary exercise Mice/f/8+ weeks Bolz et al., 2015
11 Impaired contextual fear discrimination No Yes Decreased survival and changed dendritic complexity after PS1 knockdown of adult-born neurons Mice/m/8 months Bonds et al., 2015
12 Improved spontaneous location recognition memory Yes Yes Increased NG after systemic ghrelin administration Rats/m/8+ weeks Kent et al., 2015
13 Impaired performance on a spatial metric task and temporal object association task No Yes Decreased NG in DNMT-1 knockout mice Mice/m/1–3 months Kesner et al., 2014
14 Impaired performance on similar and dissimilar trials in the location discrimination task during reversal only. Yes No Decreased NG in GFAP-TK mice Mice/m/8+ weeks Swan et al., 2014
15 Impaired object-in-place memory No Yes Decreased NG due to inflammatory factors (and normalization through ibuprofen treatment) Mice/f/8+ weeks Llorens-Martin et al., 2014
16 Impaired spontaneous location recognition memory Yes Yes Decreased NG through viral delivery of Wnt Rats/m/8+ weeks Bekinschtein et al.,2014
17 Impaired contextual fear discrimination (use of randomized and non-randomized version) No Yes Decreased NG (dorsal versus ventral) through X-ray irradiation Mice/m/7+ weeks Wu and Hen, 2014
18 Impaired contextual fear discrimination and subsequent normalization No Yes Decreased NG (Btg1 mice) and normalization using voluntary exercise Mice/-/8+ weeks Farioli-Vecchioli et al., 2014
19 Impaired DNMTP in the radial arm maze at both small and large separations Yes Yes Decreased NG in Ezh2knockout mice Mice/m/- Zhang et al., 2014
20 More perseverance in the Morris water maze, less precise search patterns. No Yes Decreased NG in Cyclin-D2 knockout mice Mice/f/8+ weeks Garthe et al., 2014
21 Impaired contextual fear discrimination (reported in separate study: Jin et al., 2013) No Yes Decreased NG in Ras/Grf1 knockout mice Mice/-/- Darcy et al., 2014 (Jin et al., 2013)
22 No effect on contextual fear discrimination No No Increased NG in Pet knockout mice (serotonin depletion) Mice/m/8–10 weeks Diaz et al., 2013
23 No effect on DNMTP in the radial arm maze at small or large separations Yes No Decreased NG in GFAP-TK rats Rats/m/8 weeks Groves et al., 2013
24 Impaired performance on small separation in touchscreen location discrimination Yes Yes Decreased NG in TNiK knockout mice Mice/m/8+ weeks Coba et al., 2012
25 Impaired and improved novel object in place memory Yes Yes Decreased NG in SREB2 transgenic mice/ Increased NG in SREB2 knockout mice Mice/m/4–6 months Chen et al., 2012
26 Impaired cognitive flexibility No Yes Decreased NG in GFAP-TK mice and after X-ray irradiation Mice/m/10+ weeks Burghardt et al., 2012
27 Impaired contextual fear discrimination Yes, in a separate experiment Yes Deletion of NR2B of the NMDAR in adult born neurons only; Mice/m/14–16 weeks Kheirbek et al., 2012
28 Impaired contextual fear discrimination after NG ablation (main finding: improved performance upon inhibited neurotransmission of adult cells) Yes, in a separate experiment Yes Inhibited neurotransmission of adult granule cells in combination with decreased NG after X-ray irradiation. Mice/m/14+ weeks Nakashiba et al., 2012
29 Impaired performance on a high interference odor discrimination paradigm No Yes Decreased NG after X-ray irradiation Rats/m/3+ months Luu et al., 2012
30 Impaired DNMTP in the radial arm maze at both small and large separations Yes Yes Decreased NG in ERK5 inducable knockout (adult born neurons only) Mice/m/12 weeks Pan et al., 2012
31 Improved contextual fear discrimination in males, no effect in females No No Ablation of postnatal NG in DNMT1 knockout mice Mice/m and f/ 3–5 months Cushman et al., 2012
32 Impaired contextual fear conditioning Yes Yes Ablation of NG using HSV-tk under the nestin promotor and by means of systemic temozolomide treatment Mice/m/10 weeks Niibori et al., 2012
33 Impaired performance on an adapted version of the Barnes’ maze No Yes NF-kB knockout results in a (pathological) increase in NG Mice/m/- Imielski et al., 2012
34 Improved performance in a submerged radial arm maze (and a lack thereof in knockout animals) Yes Yes Increased NG in control animals after enrichment; and a lack thereof in mice with conditional knock-out of CREB binding protein Mice/f/2–5 months(?) Lopez-Atalaya et al., 2011
35 Improved (and impaired) contextual fear discrimination (normal absence of fear memory in novel context) No Yes Increase (and decrease) in NG through genetic manipulation and X-ray irradiation. Mice/m and f/14–18 weeks Sahay et al., 2011
36 Impaired contextual fear discrimination No Yes Decreased NG in Nestin rtTA/Tet mice Mice/m/8 weeks Tronel et al., 2010
37 Improved location discrimination learning (touchscreen) Yes Yes Increased NG after running Mice/m/3 and 22 months Creer et al., 2010
38 Improved location discrimination learning and improved DNMTP in the radial arm maze (on similar conditions only) Yes Yes Decreased NG after X-ray irradiation and viral delivery of Wnt knockdown Mice/f/8+ weeks Clelland et al., 2009
Tab.1  Empirical animal studies of neurogenesis and pattern separation
Fig.1  Pattern separation task examples. (A) Contextual fear discrimination in which animals are trained to discriminate context A (paired with a foot shock) from a safe context (B) Delayed non-matching to location in the radial arm maze. Trial example (top): during the sample phase animals collect a reward from one arm (sample arm) and after a delay, are required to choose between the sample arm (incorrect, unbaited) and a novel arm (correct, baited) during the choice phase. Below, three different choice phase configurations are shown, taxing similarity between the sample arm and novel arm by presenting them at different separations (2, 3 or 4). Note; arms and locations should vary between trials. S= start arm. (C) The spontaneous location recognition paradigm for pattern separation. Animals explore three identical copies (A1, A2, A3) of objects during a sample phase (left) and after a delay, memory is assessed using preference for the object placed in a novel location (A5) compared to the familiar location (A4) in the choice phase (right). Two trial types are used in randomized order, implementing a small or large distance between objects A2 and A3 thereby varying pattern separation load. (Figures drawn based on task descriptions in Tronel et al., 2012; Clelland et al., 2009 and Bekinschtein et al., 2013.)
1 Abrous D N, Koehl M, Le Moal M (2005). Adult neurogenesis: from precursors to network and physiology. Physiol Rev, 85(2): 523–569
doi: 10.1152/physrev.00055.2003 pmid: 15788705
2 Aimone J B, Deng W, Gage F H (2010). Adult neurogenesis: integrating theories and separating functions. Trends Cogn Sci, 14(7): 325–337
doi: 10.1016/j.tics.2010.04.003 pmid: 20471301
3 Aimone J B, Wiles J, Gage F H (2006). Potential role for adult neurogenesis in the encoding of time in new memories. Nat Neurosci, 9(6): 723–727
doi: 10.1038/nn1707 pmid: 16732202
4 Aimone J B, Wiles J, Gage F H (2009). Computational influence of adult neurogenesis on memory encoding. Neuron, 61(2): 187–202
doi: 10.1016/j.neuron.2008.11.026 pmid: 19186162
5 Akers K G, Martinez-Canabal A, Restivo L, Yiu A P, De Cristofaro A, Hsiang H L, Wheeler A L, Guskjolen A, Niibori Y, Shoji H, Ohira K, Richards B A, Miyakawa T, Josselyn S A, Frankland P W (2014). Hippocampal neurogenesis regulates forgetting during adulthood and infancy. Science, 344(6184): 598–602
doi: 10.1126/science.1248903 pmid: 24812394
6 Alme C B, Buzzetti R A, Marrone D F, Leutgeb J K, Chawla M K, Schaner M J, Bohanick J D, Khoboko T, Leutgeb S, Moser E I, Moser M B, McNaughton B L, Barnes C A (2010). Hippocampal granule cells opt for early retirement. Hippocampus, 20(10): 1109–1123
doi: 10.1002/hipo.20810 pmid: 20872737
7 Altman J (1962). Are new neurons formed in the brains of adult mammals? Science, 135(3509): 1127–1128
doi: 10.1126/science.135.3509.1127 pmid: 13860748
8 Altman J (1969). Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. J Comp Neurol, 137(4): 433–457
doi: 10.1002/cne.901370404 pmid: 5361244
9 Bakker A, Kirwan C B, Miller M, Stark C E (2008). Pattern separation in the human hippocampal CA3 and dentate gyrus. Science, 319(5870): 1640–1642
doi: 10.1126/science.1152882 pmid: 18356518
10 Barense M D, Bussey T J, Lee A C, Rogers T T, Davies R R, Saksida L M, Murray E A, Graham K S (2005). Functional specialization in the human medial temporal lobe. J Neurosci, 25(44): 10239–10246
doi: 10.1523/JNEUROSCI.2704-05.2005 pmid: 16267231
11 Becker S (2005). A computational principle for hippocampal learning and neurogenesis. Hippocampus, 15(6): 722–738
doi: 10.1002/hipo.20095 pmid: 15986407
12 Bekinschtein P, Kent B A, Oomen C A, Clemenson G D, Gage F H, Saksida L M, Bussey T J (2014). Brain-derived neurotrophic factor interacts with adult-born immature cells in the dentate gyrus during consolidation of overlapping memories. Hippocampus, 24(8): 905–911
13 Bekinschtein P, Kent B A, Oomen C A, Clemenson G D, Gage, F H, Jr., Saksida L M, Bussey T J(2013). BDNF in the Dentate Gyrus Is Required for Consolidation of “Pattern-Separated” Memories. Cell Reports, 5: 1–10
14 Bekinschtein P, Oomen C A, Saksida L M, Bussey T J (2011). Effects of environmental enrichment and voluntary exercise on neurogenesis, learning and memory, and pattern separation: BDNF as a critical variable? Semin Cell Dev Biol, 22(5): 536–542
doi: 10.1016/j.semcdb.2011.07.002 pmid: 21767656
15 Besnard A, Sahay A (2016). Adult Hippocampal Neurogenesis, Fear Generalization, and Stress. Neuropsychopharmacology, 41(1): 24–44
doi: 10.1038/npp.2015.167 pmid: 26068726
16 Bolz L, Heigele S, Bischofberger J (2015). Running improves pattern separation during novel object recognition. Br Plast, 1(1): 129–141
doi: 10.3233/BPL-150010
17 Bonds J A, Kuttner-Hirshler Y, Bartolotti N, Tobin M K, Pizzi M, Marr R, Lazarov O (2015). Presenilin-1 Dependent Neurogenesis Regulates Hippocampal Learning and Memory. PLoS ONE, 10(6): e0131266
doi: 10.1371/journal.pone.0131266 pmid: 26098332
18 Burghardt N S, Park E H, Hen R, Fenton A A (2012). Adult-born hippocampal neurons promote cognitive flexibility in mice. Hippocampus, 22(9): 1795–1808
doi: 10.1002/hipo.22013 pmid: 22431384
19 Chen C, Shen F Y, Zhao X, Zhou T, Xu D J, Wang Z R, Wang Y W (2015). Low-dose sevoflurane promotes hippocampal neurogenesis and facilitates the development of dentate gyrus-dependent learning in neonatal rats. ASN Neuro, 7(2): 7
doi: 10.1177/1759091415575845 pmid: 25873307
20 Chen Q, Kogan J H, Gross A K, Zhou Y, Walton N M, Shin R, Heusner C L, Miyake S, Tajinda K, Tamura K, Matsumoto M (2012). SREB2/GPR85, a schizophrenia risk factor, negatively regulates hippocampal adult neurogenesis and neurogenesis-dependent learning and memory. Eur J Neurosci, 36(5): 2597–2608
doi: 10.1111/j.1460-9568.2012.08180.x pmid: 22697179
21 Clelland C D, Choi M, Romberg C, Clemenson G D Jr, Fragniere A, Tyers P, Jessberger S, Saksida L M, Barker R A, Gage F H, Bussey T J (2009). A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science, 325(5937): 210–213
doi: 10.1126/science.1173215 pmid: 19590004
22 Coba M P, Komiyama N H, Nithianantharajah J, Kopanitsa M V, Indersmitten T, Skene N G, Tuck E J, Fricker D G, Elsegood K A, Stanford L E, Afinowi N O, Saksida L M, Bussey T J, O’Dell T J, Grant S G (2012). TNiK is required for postsynaptic and nuclear signaling pathways and cognitive function. J Neurosci, 32(40): 13987–13999
doi: 10.1523/JNEUROSCI.2433-12.2012 pmid: 23035106
23 Cowell R A, Bussey T J, Saksida L M (2010). Components of recognition memory: dissociable cognitive processes or just differences in representational complexity? Hippocampus, 20(11): 1245–1262
doi: 10.1002/hipo.20865 pmid: 20882548
24 Creer D J, Romberg C, Saksida L M, van Praag H, Bussey T J (2010). Running enhances spatial pattern separation in mice. Proc Natl Acad Sci USA, 107(5): 2367–2372
doi: 10.1073/pnas.0911725107 pmid: 20133882
25 Cushman J D, Maldonado J, Kwon E E, Garcia A D, Fan G, Imura T, Sofroniew M V, Fanselow M S (2012). Juvenile neurogenesis makes essential contributions to adult brain structure and plays a sex-dependent role in fear memories. Front Behav Neurosci, 6: 3
doi: 10.3389/fnbeh.2012.00003 pmid: 22347173
26 Das T, Ivleva E I, Wagner A D, Stark C E, Tamminga C A (2014). Loss of pattern separation performance in schizophrenia suggests dentate gyrus dysfunction. Schizophr Res, 159(1): 193–197
doi: 10.1016/j.schres.2014.05.006 pmid: 25176349
27 Deisseroth K, Singla S, Toda H, Monje M, Palmer T D, Malenka R C (2004). Excitation-neurogenesis coupling in adult neural stem/progenitor cells. Neuron, 42(4): 535–552
doi: 10.1016/S0896-6273(04)00266-1 pmid: 15157417
28 Deng W, Aimone J B, Gage F H (2010). New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci, 11(5): 339–350
doi: 10.1038/nrn2822 pmid: 20354534
29 Diaz S L, Narboux-Nême N, Trowbridge S, Scotto-Lomassese S, Kleine Borgmann F B, Jessberger S, Giros B, Maroteaux L, Deneris E, Gaspar P (2013). Paradoxical increase in survival of newborn neurons in the dentate gyrus of mice with constitutive depletion of serotonin. Eur J Neurosci, 38(5): 2650–2658
doi: 10.1111/ejn.12297 pmid: 23841816
30 Dupret D, Fabre A, Döbrössy M D, Panatier A, Rodríguez J J, Lamarque S, Lemaire V, Oliet S H, Piazza P V, Abrous D N (2007). Spatial learning depends on both the addition and removal of new hippocampal neurons. PLoS Biol, 5(8): e214
doi: 10.1371/journal.pbio.0050214 pmid: 17683201
31 Efstathopoulos P, Kourgiantaki A, Karali K, Sidiropoulou K, Margioris A N, Gravanis A, Charalampopoulos I (2015). Fingolimod induces neurogenesis in adult mouse hippocampus and improves contextual fear memory. Transl Psychiatry, 5(11): e685
doi: 10.1038/tp.2015.179 pmid: 26795749
32 Epp J R, Silva Mera R, Köhler S, Josselyn S A, Frankland P W (2016). Neurogenesis-mediated forgetting minimizes proactive interference. Nat Commun, 7: 10838
doi: 10.1038/ncomms10838 pmid: 26917323
33 Eriksson P S, Perfilieva E, Björk-Eriksson T, Alborn A M, Nordborg C, Peterson D A, Gage F H (1998). Neurogenesis in the adult human hippocampus. Nat Med, 4(11): 1313–1317
doi: 10.1038/3305 pmid: 9809557
34 Farioli-Vecchioli S, Mattera A, Micheli L, Ceccarelli M, Leonardi L, Saraulli D, Costanzi M, Cestari V, Rouault J P, Tirone F (2014). Running rescues defective adult neurogenesis by shortening the length of the cell cycle of neural stem and progenitor cells. Stem Cells, 32(7): 1968–1982
doi: 10.1002/stem.1679 pmid: 24604711
35 Farioli-Vecchioli S, Saraulli D, Costanzi M, Pacioni S, Cinà I, Aceti M, Micheli L, Bacci A, Cestari V, Tirone F (2008). The timing of differentiation of adult hippocampal neurons is crucial for spatial memory. PLoS Biol, 6(10): e246
doi: 10.1371/journal.pbio.0060246 pmid: 18842068
36 Frankland P W, Cestari V, Filipkowski R K, McDonald R J, Silva A J (1998). The dorsal hippocampus is essential for context discrimination but not for contextual conditioning. Behav Neurosci, 112(4): 863–874
doi: 10.1037/0735-7044.112.4.863 pmid: 9733192
37 Frankland P W, Köhler S, Josselyn S A (2013). Hippocampal neurogenesis and forgetting. Trends Neurosci, 36(9): 497–503
doi: 10.1016/j.tins.2013.05.002 pmid: 23768770
38 Garthe A, Huang Z, Kaczmarek L, Filipkowski R K, Kempermann G (2014). Not all water mazes are created equal: cyclin D2 knockout mice with constitutively suppressed adult hippocampal neurogenesis do show specific spatial learning deficits. Genes Brain Behav, 13(4): 357–364
doi: 10.1111/gbb.12130 pmid: 24602283
39 Ge S, Yang C H, Hsu K S, Ming G L, Song H (2007). A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain. Neuron, 54(4): 559–566
doi: 10.1016/j.neuron.2007.05.002 pmid: 17521569
40 Gilbert P E, Kesner R P (2002). The amygdala but not the hippocampus is involved in pattern separation based on reward value. Neurobiol Learn Mem, 77(3): 338–353
doi: 10.1006/nlme.2001.4033 pmid: 11991762
41 Gilbert P E, Kesner R P, DeCoteau W E (1998). Memory for spatial location: role of the hippocampus in mediating spatial pattern separation. J Neurosci, 18(2): 804–810
pmid: 9425021
42 Gilbert P E, Kesner R P, Lee I (2001). Dissociating hippocampal subregions: double dissociation between dentate gyrus and CA1. Hippocampus, 11(6): 626–636
doi: 10.1002/hipo.1077 pmid: 11811656
43 Groves J O, Leslie I, Huang G J, McHugh S B, Taylor A, Mott R, Munafò M, Bannerman D M, Flint J (2013). Ablating adult neurogenesis in the rat has no effect on spatial processing: evidence from a novel pharmacogenetic model. PLoS Genet, 9(9): e1003718
doi: 10.1371/journal.pgen.1003718 pmid: 24039591
44 Hill A S, Sahay A, Hen R (2015). Increasing Adult Hippocampal Neurogenesis is Sufficient to Reduce Anxiety and Depression-Like Behaviors. Neuropsychopharmacology, 40(10): 2368–2378
doi: 10.1038/npp.2015.85 pmid: 25833129
45 Imielski Y, Schwamborn J C, Lüningschrör P, Heimann P, Holzberg M, Werner H, Leske O, Püschel A W, Memet S, Heumann R, Israel A, Kaltschmidt C, Kaltschmidt B (2012). Regrowing the adult brain: NF-kB controls functional circuit formation and tissue homeostasis in the dentate gyrus. PLoS ONE, 7(2): e30838
doi: 10.1371/journal.pone.0030838 pmid: 22312433
46 Kannangara T S, Lucero M J, Gil-Mohapel J, Drapala R J, Simpson J M, Christie B R, van Praag H (2011). Running reduces stress and enhances cell genesis in aged mice. Neurobiol Aging, 32(12): 2279–2286
doi: 10.1016/j.neurobiolaging.2009.12.025 pmid: 20106549
47 Kempermann G (2005). Adult neurogenesis, Stem Cells and Neuronal Development in the Adult Brain. Oxford University Press, New York
48 Kent B A, Beynon A L, Hornsby A K, Bekinschtein P, Bussey T J, Davies J S, Saksida L M (2015). The orexigenic hormone acyl-ghrelin increases adult hippocampal neurogenesis and enhances pattern separation. Psychoneuroendocrinology, 51: 431–439
doi: 10.1016/j.psyneuen.2014.10.015 pmid: 25462915
49 Kent B A, Hvoslef-Eide M, Saksida L M, Bussey T J (2016). The representational-hierarchical view of pattern separation: Not just hippocampus, not just space, not just memory? Neurobiol Learn Mem, 129: 99–106
doi: 10.1016/j.nlm.2016.01.006 pmid: 26836403
50 Kesner R P (2013). An analysis of the dentate gyrus function. Behav Brain Res, 254: 1–7
doi: 10.1016/j.bbr.2013.01.012 pmid: 23348108
51 Kesner R P, Hui X, Sommer T, Wright C, Barrera V R, Fanselow M S (2014). The role of postnatal neurogenesis in supporting remote memory and spatial metric processing. Hippocampus, 24(12): 1663–1671
doi: 10.1002/hipo.22346 pmid: 25112894
52 Kheirbek M A, Klemenhagen K C, Sahay A, Hen R (2012a). Neurogenesis and generalization: a new approach to stratify and treat anxiety disorders. Nat Neurosci, 15(12): 1613–1620
doi: 10.1038/nn.3262 pmid: 23187693
53 Kheirbek M A, Tannenholz L, Hen R (2012b). NR2B-dependent plasticity of adult-born granule cells is necessary for context discrimination. J Neurosci, 32(25): 8696–8702
doi: 10.1523/JNEUROSCI.1692-12.2012 pmid: 22723709
54 Kitamura T, Saitoh Y, Takashima N, Murayama A, Niibori Y, Ageta H, Sekiguchi M, Sugiyama H, Inokuchi K (2009). Adult neurogenesis modulates the hippocampus-dependent period of associative fear memory. Cell, 139(4): 814–827
doi: 10.1016/j.cell.2009.10.020 pmid: 19914173
55 Koehl M, Abrous D N (2011). A new chapter in the field of memory: adult hippocampal neurogenesis. Eur J Neurosci, 33(6): 1101–1114
doi: 10.1111/j.1460-9568.2011.07609.x pmid: 21395854
56 Leutgeb J K, Leutgeb S, Moser M B, Moser E I (2007). Pattern separation in the dentate gyrus and CA3 of the hippocampus. Science, 315(5814): 961–966
doi: 10.1126/science.1135801 pmid: 17303747
57 Liu K Y, Gould R L, Coulson M C, Ward E V, Howard R J (2016). Tests of pattern separation and pattern completion in humans-A systematic review. Hippocampus, 26(6): 705–717
doi: 10.1002/hipo.22561 pmid: 26663362
58 Llorens-Martín M, Jurado-Arjona J, Fuster-Matanzo A, Hernández F, Rábano A, Ávila J (2014). Peripherally triggered and GSK-3β-driven brain inflammation differentially skew adult hippocampal neurogenesis, behavioral pattern separation and microglial activation in response to ibuprofen. Transl Psychiatry, 4(10): e463
doi: 10.1038/tp.2014.92 pmid: 25313506
59 Lopez-Atalaya J P, Ciccarelli A, Viosca J, Valor L M, Jimenez-Minchan M, Canals S, Giustetto M, Barco A (2011). CBP is required for environmental enrichment-induced neurogenesis and cognitive enhancement. EMBO J, 30(20): 4287–4298
doi: 10.1038/emboj.2011.299 pmid: 21847097
60 Luu P, Sill O C, Gao L, Becker S, Wojtowicz J M, Smith D M (2012). The role of adult hippocampal neurogenesis in reducing interference. Behav Neurosci, 126(3): 381–391
doi: 10.1037/a0028252 pmid: 22642883
61 Marín-Burgin A, Mongiat L A, Pardi M B, Schinder A F (2012). Unique processing during a period of high excitation/inhibition balance in adult-born neurons. Science, 335(6073): 1238–1242
doi: 10.1126/science.1214956 pmid: 22282476
62 Marín-Burgin A, Schinder A F (2012). Requirement of adult-born neurons for hippocampus-dependent learning. Behav Brain Res, 227(2): 391–399
doi: 10.1016/j.bbr.2011.07.001 pmid: 21763727
63 Marr D (1971). Simple memory: a theory for archicortex. Philos Trans R Soc Lond B Biol Sci, 262(841): 23–81
doi: 10.1098/rstb.1971.0078 pmid: 4399412
64 McHugh T J, Jones M W, Quinn J J, Balthasar N, Coppari R, Elmquist J K, Lowell B B, Fanselow M S, Wilson M A, Tonegawa S (2007). Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network. Science, 317(5834): 94–99
doi: 10.1126/science.1140263 pmid: 17556551
65 McNaughton B L, Morris R G M (1987). Hippocampal synaptic enhancement and information storage within a distributed memory system. Trends Neurosci, 10(10): 408–415
doi: 10.1016/0166-2236(87)90011-7
66 Nadel L, Peterson M A (2013). The hippocampus: part of an interactive posterior representational system spanning perceptual and memorial systems. J Exp Psychol Gen, 142(4): 1242–1254
doi: 10.1037/a0033690 pmid: 23895347
67 Nakashiba T, Cushman J D, Pelkey K A, Renaudineau S, Buhl D L, McHugh T J, Rodriguez Barrera V, Chittajallu R, Iwamoto K S, McBain C J, Fanselow M S, Tonegawa S (2012). Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion. Cell, 149(1): 188–201
doi: 10.1016/j.cell.2012.01.046 pmid: 22365813
68 Neunuebel J P, Knierim J J (2014). CA3 retrieves coherent representations from degraded input: direct evidence for CA3 pattern completion and dentate gyrus pattern separation. Neuron, 81(2): 416–427
doi: 10.1016/j.neuron.2013.11.017 pmid: 24462102
69 Niibori Y, Yu T S, Epp J R, Akers K G, Josselyn S A, Frankland P W (2012). Suppression of adult neurogenesis impairs population coding of similar contexts in hippocampal CA3 region. Nat Commun, 3: 1253
doi: 10.1038/ncomms2261 pmid: 23212382
70 Oomen C A, Bekinschtein P, Kent B A, Saksida L M, Bussey T J (2014). Adult hippocampal neurogenesis and its role in cognition. Wiley Interdiscip Rev Cogn Sci, 5(5): 573–587
doi: 10.1002/wcs.1304 pmid: 26308746
71 Pan Y W, Chan G C, Kuo C T, Storm D R, Xia Z (2012). Inhibition of adult neurogenesis by inducible and targeted deletion of ERK5 mitogen-activated protein kinase specifically in adult neurogenic regions impairs contextual fear extinction and remote fear memory. J Neurosci, 32(19): 6444–6455
doi: 10.1523/JNEUROSCI.6076-11.2012 pmid: 22573667
72 Park H, Yang J, Kim R, Li Y, Lee Y, Lee C, Park J, Lee D, Kim H, Kim E (2015). Mice lacking the PSD-95-interacting E3 ligase, Dorfin/Rnf19a, display reduced adult neurogenesis, enhanced long-term potentiation, and impaired contextual fear conditioning. Sci Rep, 5: 16410
doi: 10.1038/srep16410 pmid: 26553645
73 Pérez-García G, Guzmán-Quevedo O, Da Silva Aragão R, Bolaños-Jiménez F (2016). Early malnutrition results in long-lasting impairments in pattern-separation for overlapping novel object and novel location memories and reduced hippocampal neurogenesis. Sci Rep, 6: 21275
doi: 10.1038/srep21275 pmid: 26882991
74 Rangel L M, Alexander A S, Aimone J B, Wiles J, Gage F H, Chiba A A, Quinn L K (2014). Temporally selective contextual encoding in the dentate gyrus of the hippocampus. Nat Commun, 5: 3181
doi: 10.1038/ncomms4181 pmid: 24518986
75 Revest J M, Dupret D, Koehl M, Funk-Reiter C, Grosjean N, Piazza P V, Abrous D N (2009). Adult hippocampal neurogenesis is involved in anxiety-related behaviors. Mol Psychiatry, 14(10): 959–967
doi: 10.1038/mp.2009.15 pmid: 19255582
76 Sahay A, Scobie K N, Hill A S, O’Carroll C M, Kheirbek M A, Burghardt N S, Fenton A A, Dranovsky A, Hen R (2011). Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature, 472(7344): 466–470
doi: 10.1038/nature09817 pmid: 21460835
77 Saksida L M, Bussey T J, Buckmaster C A, Murray E A (2006). No effect of hippocampal lesions on perirhinal cortex-dependent feature-ambiguous visual discriminations. Hippocampus, 16(4): 421–430
doi: 10.1002/hipo.20170 pmid: 16463387
78 Saksida L M, Bussey T J, Buckmaster C A, Murray E A (2007). Impairment and facilitation of transverse patterning after lesions of the perirhinal cortex and hippocampus, respectively. Cereb Cortex, 17(1): 108–115
doi: 10.1093/cercor/bhj128 pmid: 16452641
79 Schmidt-Hieber C, Jonas P, Bischofberger J (2004). Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature, 429(6988): 184–187
doi: 10.1038/nature02553 pmid: 15107864
80 Segal S K, Stark S M, Kattan D, Stark C E, Yassa M A (2012). Norepinephrine-mediated emotional arousal facilitates subsequent pattern separation. Neurobiol Learn Mem, 97(4): 465–469
doi: 10.1016/j.nlm.2012.03.010 pmid: 22498686
81 Seo D O, Carillo M A, Chih-Hsiung Lim S, Tanaka K F, Drew M R (2015). Adult Hippocampal Neurogenesis Modulates Fear Learning through Associative and Nonassociative Mechanisms. J Neurosci, 35(32): 11330–11345
doi: 10.1523/JNEUROSCI.0483-15.2015 pmid: 26269640
82 Shors T J, Miesegaes G, Beylin A, Zhao M, Rydel T, Gould E (2001). Neurogenesis in the adult is involved in the formation of trace memories. Nature, 410(6826): 372–376
doi: 10.1038/35066584 pmid: 11268214
83 Shors T J, Townsend D A, Zhao M, Kozorovitskiy Y, Gould E (2002). Neurogenesis may relate to some but not all types of hippocampal-dependent learning. Hippocampus, 12(5): 578–584
doi: 10.1002/hipo.10103 pmid: 12440573
84 Sisti H M, Glass A L, Shors T J (2007). Neurogenesis and the spacing effect: learning over time enhances memory and the survival of new neurons. Learn Mem, 14(5): 368–375
doi: 10.1101/lm.488707 pmid: 17522028
85 Stark S M, Stevenson R, Wu C, Rutledge S, Stark C E (2015). Stability of age-related deficits in the mnemonic similarity task across task variations. Behav Neurosci, 129(3): 257–268
doi: 10.1037/bne0000055 pmid: 26030427
86 Stark S M, Yassa M A, Stark C E (2010). Individual differences in spatial pattern separation performance associated with healthy aging in humans. Learn Mem, 17(6): 284–288
doi: 10.1101/lm.1768110 pmid: 20495062
87 Svensson M, Grahm M, Ekstrand J, Movahed-Rad P, Johansson M, Tingström A (2015). Effect of electroconvulsive seizures on pattern separation. Hippocampus, 25(11): 1351–1360
doi: 10.1002/hipo.22441 pmid: 25850383
88 Swan A A, Clutton J E, Chary P K, Cook S G, Liu G G, Drew M R (2014). Characterization of the role of adult neurogenesis in touch-screen discrimination learning. Hippocampus, 24(12): 1581–1591
doi: 10.1002/hipo.22337 pmid: 25074617
89 Treves A, Rolls E T (1992). Computational constraints suggest the need for two distinct input systems to the hippocampal CA3 network. Hippocampus, 2(2): 189–199
doi: 10.1002/hipo.450020209 pmid: 1308182
90 Treves A, Tashiro A, Witter M P, Moser E I (2008). What is the mammalian dentate gyrus good for? Neuroscience, 154(4): 1155–1172
doi: 10.1016/j.neuroscience.2008.04.073 pmid: 18554812
91 Tronel S, Belnoue L, Grosjean N, Revest J M, Piazza P V, Koehl M, Abrous D N (2012). Adult-born neurons are necessary for extended contextual discrimination. Hippocampus, 22(2): 292–298
doi: 10.1002/hipo.20895 pmid: 21049483
92 Van der Borght K, Havekes R, Bos T, Eggen B J, Van der Zee E A (2007). Exercise improves memory acquisition and retrieval in the Y-maze task: relationship with hippocampal neurogenesis. Behav Neurosci, 121(2): 324–334
doi: 10.1037/0735-7044.121.2.324 pmid: 17469921
93 Winocur G, Wojtowicz J M, Tannock I F (2015). Memory loss in chemotherapy-treated rats is exacerbated in high-interference conditions and related to suppression of hippocampal neurogenesis. Behav Brain Res, 281: 239–244
doi: 10.1016/j.bbr.2014.12.028 pmid: 25529185
94 Wu M V, Hen R (2014). Functional dissociation of adult-born neurons along the dorsoventral axis of the dentate gyrus. Hippocampus, 24(7): 751–761
doi: 10.1002/hipo.22265 pmid: 24550158
95 Wu M V, Luna V M, Hen R (2015). Running rescues a fear-based contextual discrimination deficit in aged mice. Front Syst Neurosci, 9: 114
doi: 10.3389/fnsys.2015.00114 pmid: 26321926
96 Yagi S, Chow C, Lieblich S E, Galea L A (2016). Sex and strategy use matters for pattern separation, adult neurogenesis, and immediate early gene expression in the hippocampus. Hippocampus, 26(1): 87–101
doi: 10.1002/hipo.22493 pmid: 26179150
97 Yassa M A, Muftuler L T, Stark C E (2010). Ultrahigh-resolution microstructural diffusion tensor imaging reveals perforant path degradation in aged humans in vivo. Proc Natl Acad Sci USA, 107(28): 12687–12691
doi: 10.1073/pnas.1002113107 pmid: 20616040
98 Yassa M A, Stark C E (2011). Pattern separation in the hippocampus. Trends Neurosci, 34(10): 515–525
doi: 10.1016/j.tins.2011.06.006 pmid: 21788086
99 Yun S, Donovan M H, Ross M N, Richardson D R, Reister R, Farnbauch L A, Fischer S J, Riethmacher D, Gershenfeld H K, Lagace D C, Eisch A J (2016). Stress-induced anxiety- and depressive-like phenotype associated with transient reduction in neurogenesis in adult nestin-CreERT2/Diphtheria toxin fragment A transgenic mice. PLoS ONE, 11(1): e0147256
doi: 10.1371/journal.pone.0147256 pmid: 26795203
100 Zhang C L, Zou Y, He W, Gage F H, Evans R M (2008). A role for adult TLX-positive neural stem cells in learning and behaviour. Nature, 451(7181): 1004–1007
doi: 10.1038/nature06562 pmid: 18235445
101 Zhang J, Ji F, Liu Y, Lei X, Li H, Ji G, Yuan Z, Jiao J (2014). Ezh2 regulates adult hippocampal neurogenesis and memory. J Neurosci, 34(15): 5184–5199
doi: 10.1523/JNEUROSCI.4129-13.2014 pmid: 24719098
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