Adult neurogenesis and pattern separation in rodents: A critical evaluation of data, tasks and interpretation
Received date: 22 Mar 2016
Accepted date: 20 May 2016
Published date: 05 Jul 2016
Copyright
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.
Key words： adult neurogenesis; memory; pattern separation; dentate gyrus; behavioral paradigms
Martha Hvoslef-Eide , Charlotte A. Oomen . Adult neurogenesis and pattern separation in rodents: A critical evaluation of data, tasks and interpretation[J]. Frontiers in Biology, 2016 , 11(3) : 168 -181 . DOI: 10.1007/s11515-016-1406-2
| 1 |
Abrous D N, Koehl M, Le Moal M (2005). Adult neurogenesis: from precursors to network and physiology. Physiol Rev, 85(2): 523–569
|
| 2 |
Aimone J B, Deng W, Gage F H (2010). Adult neurogenesis: integrating theories and separating functions. Trends Cogn Sci, 14(7): 325–337
|
| 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
|
| 4 |
Aimone J B, Wiles J, Gage F H (2009). Computational influence of adult neurogenesis on memory encoding. Neuron, 61(2): 187–202
|
| 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
|
| 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
|
| 7 |
Altman J (1962). Are new neurons formed in the brains of adult mammals? Science, 135(3509): 1127–1128
|
| 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
|
| 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
|
| 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
|
| 11 |
Becker S (2005). A computational principle for hippocampal learning and neurogenesis. Hippocampus, 15(6): 722–738
|
| 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,
|
| 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
|
| 15 |
Besnard A, Sahay A (2016). Adult Hippocampal Neurogenesis, Fear Generalization, and Stress. Neuropsychopharmacology, 41(1): 24–44
|
| 16 |
Bolz L, Heigele S, Bischofberger J (2015). Running improves pattern separation during novel object recognition. Br Plast, 1(1): 129–141
|
| 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
|
| 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
|
| 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
|
| 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
|
| 21 |
Clelland C D, Choi M, Romberg C, Clemenson G D
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 37 |
Frankland P W, Köhler S, Josselyn S A (2013). Hippocampal neurogenesis and forgetting. Trends Neurosci, 36(9): 497–503
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 50 |
Kesner R P (2013). An analysis of the dentate gyrus function. Behav Brain Res, 254: 1–7
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 62 |
Marín-Burgin A, Schinder A F (2012). Requirement of adult-born neurons for hippocampus-dependent learning. Behav Brain Res, 227(2): 391–399
|
| 63 |
Marr D (1971). Simple memory: a theory for archicortex. Philos Trans R Soc Lond B Biol Sci, 262(841): 23–81
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 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
|
| 98 |
Yassa M A, Stark C E (2011). Pattern separation in the hippocampus. Trends Neurosci, 34(10): 515–525
|
| 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
|
| 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
|
| 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
|
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| 〈 |
|
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