Frontiers in Biology

, Volume 11, Issue 3, pp 168–181 | Cite as

Adult neurogenesis and pattern separation in rodents: A critical evaluation of data, tasks and interpretation

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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 
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References

  1. Abrous D N, Koehl M, Le Moal M (2005). Adult neurogenesis: from precursors to network and physiology. Physiol Rev, 85(2): 523–569PubMedCrossRefGoogle Scholar
  2. Aimone J B, Deng W, Gage F H (2010). Adult neurogenesis: integrating theories and separating functions. Trends Cogn Sci, 14 (7): 325–337PubMedPubMedCentralCrossRefGoogle Scholar
  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): 723–727PubMedCrossRefGoogle Scholar
  4. Aimone J B, Wiles J, Gage F H (2009). Computational influence of adult neurogenesis on memory encoding. Neuron, 61(2): 187–202PubMedPubMedCentralCrossRefGoogle Scholar
  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): 598–602PubMedCrossRefGoogle Scholar
  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): 1109–1123PubMedCrossRefGoogle Scholar
  7. Altman J (1962). Are new neurons formed in the brains of adult mammals? Science, 135(3509): 1127–1128PubMedCrossRefGoogle Scholar
  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): 433–457PubMedGoogle Scholar
  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): 1640–1642PubMedPubMedCentralCrossRefGoogle Scholar
  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): 10239–10246PubMedCrossRefGoogle Scholar
  11. Becker S (2005). A computational principle for hippocampal learning and neurogenesis. Hippocampus, 15(6): 722–738PubMedCrossRefGoogle Scholar
  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): 905–911PubMedPubMedCentralCrossRefGoogle Scholar
  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: 1–10CrossRefGoogle Scholar
  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): 536–542PubMedCrossRefGoogle Scholar
  15. Besnard A, Sahay A (2016). Adult Hippocampal Neurogenesis, Fear Generalization, and Stress. Neuropsychopharmacology, 41(1): 24–44PubMedCrossRefGoogle Scholar
  16. Bolz L, Heigele S, Bischofberger J (2015). Running improves pattern separation during novel object recognition. Br Plast, 1(1): 129–141CrossRefGoogle Scholar
  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): e0131266CrossRefGoogle Scholar
  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): 1795–1808PubMedPubMedCentralCrossRefGoogle Scholar
  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): 7CrossRefGoogle Scholar
  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): 2597–2608PubMedPubMedCentralCrossRefGoogle Scholar
  21. Clelland C D, Choi M, Romberg C, Clemenson G D, Fragniere A, Tyers P, Jessberger S, Saksida LM, Barker R A, Gage F H, Bussey T J (2009). A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science, 325(5937): 210–213PubMedPubMedCentralCrossRefGoogle Scholar
  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): 13987–13999PubMedPubMedCentralCrossRefGoogle Scholar
  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): 1245–1262PubMedCrossRefGoogle Scholar
  24. Creer D J, Romberg C, Saksida LM, van Praag H, Bussey T J (2010). Running enhances spatial pattern separation in mice. Proc Natl Acad Sci USA, 107(5): 2367–2372PubMedPubMedCentralCrossRefGoogle Scholar
  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 sexdependent role in fear memories. Front Behav Neurosci, 6: 3PubMedPubMedCentralCrossRefGoogle Scholar
  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): 193–197PubMedPubMedCentralCrossRefGoogle Scholar
  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): 535–552PubMedCrossRefGoogle Scholar
  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): 339–350PubMedPubMedCentralCrossRefGoogle Scholar
  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): 2650–2658PubMedCrossRefGoogle Scholar
  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): e214CrossRefGoogle Scholar
  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): e685CrossRefGoogle Scholar
  32. Epp J R, Silva Mera R, Köhler S, Josselyn S A, Frankland PW (2016). Neurogenesis-mediated forgetting minimizes proactive interference. Nat Commun, 7: 10838PubMedPubMedCentralCrossRefGoogle Scholar
  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): 1313–1317PubMedCrossRefGoogle Scholar
  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): 1968–1982PubMedCrossRefGoogle Scholar
  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): e246CrossRefGoogle Scholar
  36. Frankland PW, 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): 863–874PubMedCrossRefGoogle Scholar
  37. Frankland P W, Köhler S, Josselyn S A (2013). Hippocampal neurogenesis and forgetting. Trends Neurosci, 36(9): 497–503PubMedCrossRefGoogle Scholar
  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): 357–364PubMedPubMedCentralCrossRefGoogle Scholar
  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): 559–566PubMedPubMedCentralCrossRefGoogle Scholar
  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): 338–353PubMedCrossRefGoogle Scholar
  41. Gilbert P E, Kesner R P, De Coteau W E (1998). Memory for spatial location: role of the hippocampus in mediating spatial pattern separation. J Neurosci, 18(2): 804–810PubMedGoogle Scholar
  42. Gilbert P E, Kesner R P, Lee I (2001). Dissociating hippocampal subregions: double dissociation between dentate gyrus and CA1. Hippocampus, 11(6): 626–636PubMedCrossRefGoogle Scholar
  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): e1003718CrossRefGoogle Scholar
  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): 2368–2378PubMedCrossRefGoogle Scholar
  45. Imielski Y, Schwamborn J C, Lüningschrör P, Heimann P, Holzberg M, Werner H, Leske O, Püschel AW, 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): e30838CrossRefGoogle Scholar
  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): 2279–2286PubMedCrossRefGoogle Scholar
  47. Kempermann G (2005). Adult neurogenesis, Stem Cells and Neuronal Development in the Adult Brain. Oxford University Press, New YorkGoogle Scholar
  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 acylghrelin increases adult hippocampal neurogenesis and enhances pattern separation. Psychoneuroendocrinology, 51: 431–439PubMedPubMedCentralCrossRefGoogle Scholar
  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: 99–106PubMedCrossRefGoogle Scholar
  50. Kesner R P (2013). An analysis of the dentate gyrus function. Behav Brain Res, 254: 1–7PubMedCrossRefGoogle Scholar
  51. Kesner R P, Hui X, Sommer T, Wright C, Barrera V R, Fanselow MS (2014). The role of postnatal neurogenesis in supporting remote memory and spatial metric processing. Hippocampus, 24(12): 1663–1671PubMedCrossRefGoogle Scholar
  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): 1613–1620PubMedPubMedCentralCrossRefGoogle Scholar
  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): 8696–8702PubMedPubMedCentralCrossRefGoogle Scholar
  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): 814–827PubMedCrossRefGoogle Scholar
  55. Koehl M, Abrous D N (2011). A new chapter in the field of memory: adult hippocampal neurogenesis. Eur J Neurosci, 33(6): 1101–1114PubMedCrossRefGoogle Scholar
  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): 961–966PubMedCrossRefGoogle Scholar
  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): 705–717PubMedCrossRefGoogle Scholar
  58. Llorens-Martín M, Jurado-Arjona J, Fuster-Matanzo A, Hernández F, Rábano A, Ávila J (2014). Peripherally triggered and GSK-3ß- driven brain inflammation differentially skew adult hippocampal neurogenesis, behavioral pattern separation and microglial activation in response to ibuprofen. Transl Psychiatry, 4 (10): e463CrossRefGoogle Scholar
  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): 4287–4298PubMedPubMedCentralCrossRefGoogle Scholar
  60. Luu P, Sill O C, Gao L, Becker S, Wojtowicz JM, Smith DM(2012). The role of adult hippocampal neurogenesis in reducing interference. Behav Neurosci, 126(3): 381–391PubMedPubMedCentralCrossRefGoogle Scholar
  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): 1238–1242PubMedPubMedCentralCrossRefGoogle Scholar
  62. Marín-Burgin A, Schinder A F (2012). Requirement of adult-born neurons for hippocampus-dependent learning. Behav Brain Res, 227 (2): 391–399PubMedCrossRefGoogle Scholar
  63. Marr D (1971). Simple memory: a theory for archicortex. Philos Trans R Soc Lond B Biol Sci, 262(841): 23–81PubMedCrossRefGoogle Scholar
  64. McHugh T J, Jones MW, 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): 94–99PubMedCrossRefGoogle Scholar
  65. McNaughton B L, Morris R G M (1987). Hippocampal synaptic enhancement and information storage within a distributed memory system. Trends Neurosci, 10(10): 408–415CrossRefGoogle Scholar
  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): 1242–1254PubMedCrossRefGoogle Scholar
  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): 188–201PubMedPubMedCentralCrossRefGoogle Scholar
  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): 416–427PubMedPubMedCentralCrossRefGoogle Scholar
  69. Niibori Y, Yu T S, Epp J R, Akers K G, Josselyn S A, Frankland PW (2012). Suppression of adult neurogenesis impairs population coding of similar contexts in hippocampal CA3 region. Nat Commun, 3: 1253PubMedPubMedCentralCrossRefGoogle Scholar
  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): 573–587PubMedPubMedCentralCrossRefGoogle Scholar
  71. Pan YW, 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): 6444–6455PubMedPubMedCentralCrossRefGoogle Scholar
  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 longterm potentiation, and impaired contextual fear conditioning. Sci Rep, 5: 16410PubMedPubMedCentralCrossRefGoogle Scholar
  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: 21275PubMedPubMedCentralCrossRefGoogle Scholar
  74. Rangel LM, 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: 3181PubMedPubMedCentralCrossRefGoogle Scholar
  75. Revest JM, 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): 959–967PubMedCrossRefGoogle Scholar
  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): 466–470PubMedPubMedCentralCrossRefGoogle Scholar
  77. Saksida L M, Bussey T J, Buckmaster C A, Murray E A (2006). No effect of hippocampal lesions on perirhinal cortex-dependent featureambiguous visual discriminations. Hippocampus, 16(4): 421–430PubMedCrossRefGoogle Scholar
  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): 108–115PubMedCrossRefGoogle Scholar
  79. Schmidt-Hieber C, Jonas P, Bischofberger J (2004). Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature, 429(6988): 184–187PubMedCrossRefGoogle Scholar
  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): 465–469PubMedPubMedCentralCrossRefGoogle Scholar
  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): 11330–11345PubMedPubMedCentralCrossRefGoogle Scholar
  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): 372–376PubMedCrossRefGoogle Scholar
  83. Shors T J, Townsend D A, Zhao M, Kozorovitskiy Y, Gould E (2002). Neurogenesis may relate to some but not all types of hippocampaldependent learning. Hippocampus, 12(5): 578–584PubMedPubMedCentralCrossRefGoogle Scholar
  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): 368–375PubMedPubMedCentralCrossRefGoogle Scholar
  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): 257–268PubMedPubMedCentralCrossRefGoogle Scholar
  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): 284–288PubMedPubMedCentralCrossRefGoogle Scholar
  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): 1351–1360PubMedCrossRefGoogle Scholar
  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 touchscreen discrimination learning. Hippocampus, 24(12): 1581–1591PubMedPubMedCentralCrossRefGoogle Scholar
  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): 189–199PubMedCrossRefGoogle Scholar
  90. Treves A, Tashiro A, Witter M P, Moser E I (2008). What is the mammalian dentate gyrus good for? Neuroscience, 154(4): 1155–1172PubMedCrossRefGoogle Scholar
  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): 292–298PubMedCrossRefGoogle Scholar
  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 Ymaze task: relationship with hippocampal neurogenesis. Behav Neurosci, 121(2): 324–334PubMedCrossRefGoogle Scholar
  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: 239–244PubMedCrossRefGoogle Scholar
  94. Wu M V, Hen R (2014). Functional dissociation of adult-born neurons along the dorsoventral axis of the dentate gyrus. Hippocampus, 24 (7): 751–761PubMedPubMedCentralCrossRefGoogle Scholar
  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: 114PubMedPubMedCentralGoogle Scholar
  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): 87–101PubMedCrossRefGoogle Scholar
  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): 12687–12691PubMedPubMedCentralCrossRefGoogle Scholar
  98. Yassa M A, Stark C E (2011). Pattern separation in the hippocampus. Trends Neurosci, 34(10): 515–525PubMedPubMedCentralCrossRefGoogle Scholar
  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): e0147256CrossRefGoogle Scholar
  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): 1004–1007PubMedCrossRefGoogle Scholar
  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): 5184–5199PubMedCrossRefGoogle Scholar

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© Higher Education Press and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Department of PsychologyUniversity of CambridgeCambridgeUK
  2. 2.Behavioural and Clinical Neuroscience InstituteUniversity of CambridgeCambridgeUK
  3. 3.Department of Cognitive NeuroscienceRadboud University Medical Center, Donders InstituteNijmegenThe Netherlands
  4. 4.Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus AmsterdamVU University Amsterdam AmsterdamHV AmsterdamThe Netherlands

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