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Review Articles

Neurogenesis in the adult hippocampus: history, regulation, and prospective roles

ORCID Icon, , &
Pages 598-611 | Received 25 Jun 2018, Accepted 03 Nov 2018, Published online: 26 Dec 2018

References

  • Ming GL, Song H. Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci. 2005;28:223–250.
  • Altman J. Are new neurons formed in the brains of adult mammals? Science. 1962;135:1127–1128.
  • Goldman SA, Nottebohm F. Neuronal production, migration, and differentiation in a vocal control nucleus of the adult female canary brain. Proc Natl Acad Sci USA. 1983;80:2390–2394.
  • Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science. 1992;255:1707–1710.
  • Kuhn HG, Dickinson-Anson H, Gage FH. Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci. 1996;16:2027–2033.
  • Eriksson PS, Perfilieva E, Björk-Eriksson T, et al. Neurogenesis in the adult human hippocampus. Nat Med. 1998;4:1313.
  • Gage FH. Mammalian neural stem cells. Science. 2000;287:1433–1438.
  • Giap BT, Jong CN, Ricker JH, et al. The hippocampus: anatomy, pathophysiology, and regenerative capacity. J Head Trauma Rehabil. 2000;1(15):875–894.
  • Llorens-Martín M, Jurado-Arjona J, Avila J, et al. Novel connection between newborn granule neurons and the hippocampal CA2 field. Exp Neurol. 2015;263:285–292.
  • Hitti FL, Siegelbaum SA. The hippocampal CA2 region is essential for social memory. Nature. 2014;508:88.
  • Wintzer ME, Boehringer R, Polygalov D, et al. The hippocampal CA2 ensemble is sensitive to contextual change. J Neurosci. 2014;34:3056–3066.
  • Gu Y, Janoschka S, Ge S. Neurogenesis and hippocampal plasticity in adult brain. In: Neurogenesis and neural plasticity. Berlin, Heidelberg: Springer; 2012. p. 31–48.
  • Temprana SG, Mongiat LA, Yang SM, et al. Delayed coupling to feedback inhibition during a critical period for the integration of adult-born granule cells. Neuron. 2015;85:116–130.
  • Leuner B, Gould E. Structural plasticity and hippocampal function. Annu Rev Psychol. 2010;61:111–140.
  • Faulkner RL, Jang MH, Liu XB, et al. Development of hippocampal mossy fiber synaptic outputs by new neurons in the adult brain. Proc Natl Acad Sci USA. 2008;105:14157.
  • Lledo PM, Alonso M, Grubb MS. Adult neurogenesis and functional plasticity in neuronal circuits. Nat Rev Neurosci. 2006;7:179.
  • Leuner B, Mendolia LS, Kozorovitskiy Y, et al. Learning enhances the survival of new neurons beyond the time when the hippocampus is required for memory. J Neurosci. 2004;24:7477–7481.
  • Deng W, Aimone JB, Gage FH. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci. 2010;11:339.
  • Ramon y Cajal S. Degeneration and regeneration of the nervous system. Oxford, England: Clarendon Press; 1928.
  • Lisman JE. Relating hippocampal circuitry to function: recall of memory sequences by reciprocal dentate-CA3 interactions. Neuron. 1999;22:233–242.
  • Shors TJ, Miesegaes G, Beylin A, et al. Neurogenesis in the adult is involved in the formation of trace memories. Nature. 2001;410:372.
  • Toni N, Laplagne DA, Zhao C, et al. Neurons born in the adult dentate gyrus form functional synapses with target cells. Nat Neurosci. 2008;11:901.
  • Gross CG. Neurogenesis in the adult brain: death of a dogma. Nat Rev Neurosci. 2000;1:67.
  • Kempermann G, Kuhn HG, Gage FH. Genetic influence on neurogenesis in the dentate gyrus of adult mice. Proc Natl Acad Sci USA. 1997;94:10409–10414.
  • Kempermann G, Kuhn HG, Gage FH. More hippocampal neurons in adult mice living in an enriched environment. Nature. 1997;386:493.
  • LaDage LD, Roth TC, Pravosudov VV. Hippocampal neurogenesis is associated with migratory behaviour in adult but not juvenile sparrows (Zonotrichia leucophrys ssp.). Proc Roy Soc Lond B: Biol Sci. 2011;278:138–143.
  • Font E, Desfilis E, Pérez-Cañellas MM, et al. Neurogenesis and neuronal regeneration in the adult reptilian brain. Brain Behav Evol. 2001;58:276–295.
  • González-Granero S, Lezameta M, García-Verdugo JM. Adult neurogenesis in reptiles. In: Neurogenesis in the adult brain I. Tokyo: Springer; 2011. p. 169–189.
  • Zupanc GK. Neurogenesis and neuronal regeneration in the adult fish brain. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2006;192:649.
  • Ganz J, Brand M. Adult neurogenesis in fish. Cold Spring Harb Perspect Biol. 2016;8:a019018.
  • Asrican B, Paez-Gonzalez P, Erb J, et al. Cholinergic circuit control of postnatal neurogenesis. Neurogenesis. 2016;3:e1127310.
  • Snyder JS, Glover LR, Sanzone KM, et al. The effects of exercise and stress on the survival and maturation of adult‐generated granule cells. Hippocampus. 2009;1;19:898–906.
  • Pilz GA, Bottes S, Betizeau M, et al. Live imaging of neurogenesis in the adult mouse hippocampus. Science. 2018;359:658–662.
  • Sorrells SF, Paredes MF, Cebrian-Silla A, et al. Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature. 2018;555:377.
  • Boldrini M, Fulmore CA, Tartt AN, et al. Human hippocampal neurogenesis persists throughout aging. Cell Stem Cell. 2018;22:589–599.
  • Grelat A, Benoit L, Wagner S, et al. Adult-born neurons boost odor–reward association. Proc Natl Acad Sci USA. 2018;115:2514–2519.
  • Kokoeva MV, Yin H, Flier JS. Neurogenesis in the hypothalamus of adult mice: potential role in energy balance. Science. 2005;310:679–683. Oct 28
  • Rojczyk-Gołębiewska E, Pałasz A, Wiaderkiewicz R. Hypothalamic subependymal niche: a novel site of the adult neurogenesis. Cell Mol Neurobiol. 2014;34:631–642.
  • Maggi R, Zasso J, Conti L. Neurodevelopmental origin and adult neurogenesis of the neuroendocrine hypothalamus. Front Cell Neurosci. 2015;8:440.
  • Kaslin J, Ganz J, Brand M. Proliferation, neurogenesis and regeneration in the non-mammalian vertebrate brain. Philos Trans Roy Soc B: Biol Sci. 2008;363:101.
  • Treves A, Tashiro A, Witter MP, et al. What is the mammalian dentate gyrus good for? Neuroscience. 2008;154:1155–1172.
  • Amrein I, Lipp HP. Adult hippocampal neurogenesis of mammals: evolution and life history. Biol Lett. 2009;5:141–144.
  • Kempermann G. New neurons for 'survival of the fittest'. Nat Rev Neurosci. 2012;13:727.
  • Rakic P. Limits of neurogenesis in primates. Science. 1985;227:1054–1056.
  • Spalding KL, Bergmann O, Alkass K, et al. Dynamics of hippocampal neurogenesis in adult humans. Cell. 2013;153:1219–1227.
  • Kosaka K, Aika Y, Toida K, et al. Chemically defined neuron groups and their subpopulations in the glomerular layer of the rat main olfactory bulb. Neurosci Res. 1995;23:73–88.
  • Pignatelli A, Gambardella C, Belluzzi O. Neurogenesis in the adult olfactory bulb. Neur Regen Res. 2011;6:575–600.
  • Merkle FT, Mirzadeh Z, Alvarez-Buylla A. Mosaic organization of neural stem cells in the adult brain. Science. 2007;317:381–384.
  • Lim DA, Alvarez-Buylla A. The adult ventricular–subventricular zone (V-SVZ) and olfactory bulb (OB) neurogenesis. Cold Spring Harb Perspect Biol. 2016;8:a018820.
  • Ernst A, Alkass K, Bernard S, et al. Neurogenesis in the striatum of the adult human brain. Cell. 2014;156:1072–1083.
  • Paredes MF, James D, Gil-Perotin S, et al. Extensive migration of young neurons into the infant human frontal lobe. Science. 2016;354:aaf7073.
  • Patzke N, Spocter MA, Bertelsen MF, et al. In contrast to many other mammals, cetaceans have relatively small hippocampi that appear to lack adult neurogenesis. Brain Struct Funct. 2015;220:361–383.
  • Drew LJ, Fusi S, Hen R. Adult neurogenesis in the mammalian hippocampus: Why the dentate gyrus? Learn Mem. 2013;20:710–729.
  • Edelman GM. Neural Darwinism: selection and reentrant signaling in higher brain function. Neuron. 1993;10:115.
  • Kolb B, Gibb R. Brain plasticity and behaviour in the developing brain. J Can Acad Child Adolesc Psychiat. 2011;20:265–276.
  • Snyder JS, Kee N, Wojtowicz JM. Effects of adult neurogenesis on synaptic plasticity in the rat dentate gyrus. J Neurophysiol. 2001;85:2423–2431.
  • Schmidt-Hieber C, Jonas P, Bischofberger J. Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature. 2004;429:184.
  • Garthe A, Behr J, Kempermann G. Adult-generated hippocampal neurons allow the flexible use of spatially precise learning strategies. PLoS One. 2009;4:e5464.
  • Wang S, Scott BW, Wojtowicz JM. Heterogenous properties of dentate granule neurons in the adult rat. J Neurobiol. 2000;42:248–257.
  • Alvarez-Buylla A. Neurogenesis and plasticity in the CNS of adult birds. Exp Neurol. 1992;115:110.
  • Nottebohm F, Nottebohm ME, Crane L. Developmental and seasonal changes in canary song and their relation to changes in the anatomy of song-control nuclei. Behav Neural Biol. 1986;46:445–471.
  • Barnea A, Nottebohm F. Seasonal recruitment of hippocampal neurons in adult free-ranging black-capped chickadees. Proc Natl Acad Sci USA. 1994;91:11217–11221.
  • Freund J, Brandmaier AM, Lewejohann L, et al. Emergence of individuality in genetically identical mice. Science. 2013;340:756–759.
  • Seress L. Comparative anatomy of the hippocampal dentate gyrus in adult and developing rodents, non-human primates and humans. Progr Brain Res. 2007;163:23–798.
  • Spalding KL, Bhardwaj RD, Buchholz BA, et al. Retrospective birth dating of cells in humans. Cell. 2005;122:133–143.
  • de Vries H. Atomic bomb effect: variation of radio-carbon in plants, shells, and snails in the past four years. Science. 1958;1:128.
  • Nydal R, Lövseth K. Distribution of radiocarbon from nuclear tests. Nature. 1965;206:1029
  • Altman J. Autoradiographic investigation of cell proliferation in the brains of rats and cats. Anat Rec. 1963;145:573–591.
  • Altman J, Das GD. Postnatal neurogenesis in the guinea-pig. Nature. 1967;214:1098.
  • Rakic P. Neurons in rhesus monkey visual cortex: systematic relation between time of origin and eventual disposition. Science. 1974;183:425–427.
  • Kaplan MS, Hinds JW. Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. Science. 1977;197:1092.
  • Kaplan MS, Hinds JW. Gliogenesis of astrocytes and oligodendrocytes in the neocortical grey and white matter of the adult rat: electron microscopic analysis of light radioautographs. J Comp Neurol. 1980;1;193:711–727.
  • Kaplan MS. Neurogenesis in the 3-month-old rat visual cortex . J Comp Neurol. 1981;195:323–338.
  • Kaplan MS, Bell DH. Mitotic neuroblasts in the 9-day-old and 11-month-old rodent hippocampus. J Neurosci. 1984;4:1429–1441.
  • Gould E, Tanapat P, McEwen BS, et al. Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proc Natl Acad Sci USA. 1998;95:3168–3171.
  • Van Praag H, Kempermann G, Gage FH. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci. 1999;2:266.
  • Gould E, Beylin A, Tanapat P, et al. Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci. 1999;2:260.
  • Gould E, Reeves AJ, Fallah M, et al. Hippocampal neurogenesis in adult Old World primates. Proc Natl Acad Sci. 1999;96:5263–5267.
  • Kornack DR, Rakic P. Continuation of neurogenesis in the hippocampus of the adult macaque monkey. Proc Natl Acad Sci USA. 1999;96:5768–5773.
  • Gould E, Reeves AJ, Graziano MS, et al. Neurogenesis in the neocortex of adult primates. Science. 1999;286:548–552.
  • Magavi SS, Leavitt BR, Macklis JD. Induction of neurogenesis in the neocortex of adult mice. Nature. 2000;405:951.
  • Malberg JE, Eisch AJ, Nestler EJ, et al. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci. 2000;20:9104.
  • Bédard A, Parent A. Evidence of newly generated neurons in the human olfactory bulb. Brain Res Dev Brain Res. 2004;151:159–168.
  • Dayer AG, Cleaver KM, Abouantoun T, et al. New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors. J Cell Biol. 2005;168:415–427.
  • Jin K, Wang X, Xie L, et al. Evidence for stroke-induced neurogenesis in the human brain. Proc Natl Acad Sci USA. 2006;103:13198–13202.
  • Tashiro A, Makino H, Gage FH. Experience-specific functional modification of the dentate gyrus through adult neurogenesis: a critical period during an immature stage. J Neurosci. 2007;27:3252–3259.
  • Jessberger S, Zhao C, Toni N, et al. Seizure-associated, aberrant neurogenesis in adult rats characterized with retrovirus-mediated cell labeling. J Neurosci. 2007;27:9400–9407. Aug 29
  • Wang JW, David DJ, Monckton JE, et al. Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells. J Neurosci. 2008;28:1374–1384.
  • Deng W, Saxe MD, Gallina IS, et al. Adult-born hippocampal dentate granule cells undergoing maturation modulate learning and memory in the brain. J Neurosci. 2009;29:13532–13542.
  • Fanselow MS, Dong HW. Are the dorsal and ventral hippocampus functionally distinct structures? Neuron. 2010;65:7–19.
  • Mu Y, Zhao C, Gage FH. Dopaminergic modulation of cortical inputs during maturation of adult-born dentate granule cells. J Neurosci. 2011;31:4113–4123.
  • Jun H, Mohammed Qasim Hussaini S, Rigby MJ, et al. Functional role of adult hippocampal neurogenesis as a therapeutic strategy for mental disorders. Neur Plast. 2012;2012:1.
  • Yassa MA, Reagh ZM. Competitive trace theory: a role for the hippocampus in contextual interference during retrieval. Front Behav Neurosci. 2013;7:107.
  • Mahar I, Bambico FR, Mechawar N, et al. Stress, serotonin, and hippocampal neurogenesis in relation to depression and antidepressant effects. Neurosci Biobehav Rev. 2014;38:173–192.
  • Ortega-Martínez S. A new perspective on the role of the CREB family of transcription factors in memory consolidation via adult hippocampal neurogenesis. Front Molec Neurosci. 2015;26:8.
  • Götz M, Nakafuku M, Petrik D. Neurogenesis in the developing and adult brain—similarities and key differences. Cold Spring Harb Perspect Biol. 2016;8:a018853.
  • Pilz GA, Carta S, Stäuble A, et al. Functional imaging of dentate granule cells in the adult mouse hippocampus. J Neurosci. 2016;36:7407–7414.
  • Castellano JM, Mosher KI, Abbey RJ, et al. Human umbilical cord plasma proteins revitalize hippocampal function in aged mice. Nature. 2017;544:488
  • Kirschen GW, Shen J, Tian M, et al. Active dentate granule cells encode experience to promote the addition of adult-born Hippocampal neurons. J Neurosci. 2017;3;37:4661–4678.
  • Danielson NB, Turi GF, Ladow M, et al. In vivo imaging of dentate gyrus mossy cells in behaving mice. Neuron. 2017;93:552–559.
  • Alenina N, Klempin F. The role of serotonin in adult hippocampal neurogenesis. Behav Brain Res. 2015;277:49–57.
  • Heigele S, Sultan S, Toni N, et al. Bidirectional GABAergic control of action potential firing in newborn hippocampal granule cells. Nat Neurosci. 2016;19:263.
  • Alvarez DD, Giacomini D, Yang SM, et al. A disynaptic feedback network activated by experience promotes the integration of new granule cells. Science. 2016;354:459–465.
  • Dumitru I, Neitz A, Alfonso J, et al. Diazepam binding inhibitor promotes stem cell expansion controlling environment-dependent neurogenesis. Neuron. 2017;94:125.
  • Apple DM, Fonseca RS, Kokovay E. The role of adult neurogenesis in psychiatric and cognitive disorders. Brain Res. 2017;1655:270–276.
  • Imayoshi I, Sakamoto M, Ohtsuka T, et al. Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain. Nat Neurosci. 2008;11:1153.
  • Imayoshi I, Kageyama R. bHLH factors in self-renewal, multipotency, and fate choice of neural progenitor cells. Neuron. 2014;82:9–23.
  • Genander M, Frisén J. Ephrins and Eph receptors in stem cells and cancer. Curr Opin Cell Biol. 2010;22:611–616.
  • Ahn S, Joyner AL. In vivo analysis of quiescent adult neural stem cells responding to Sonic hedgehog. Nature. 2005;437:894.
  • Balordi F, Fishell G. Mosaic removal of hedgehog signaling in the adult SVZ reveals that the residual wild-type stem cells have a limited capacity for self-renewal. J Neurosci. 2007;27:14248–14259.
  • Lie DC, Colamarino SA, Song HJ, et al. Wnt signalling regulates adult hippocampal neurogenesis. Nature. 2005;437:1370.
  • Gonçalves JT, Schafer ST, Gage FH. Adult neurogenesis in the hippocampus: from stem cells to behavior. Cell. 2016;167:897–914.
  • Bonaguidi MA, McGuire T, Hu M, et al. LIF and BMP signaling generate separate and discrete types of GFAP-expressing cells. Development. 2005;132:5503–5514.
  • Mira H, Andreu Z, Suh H, et al. Signaling through BMPR-IA regulates quiescence and long-term activity of neural stem cells in the adult hippocampus. Cell Stem Cell. 2010;7:78–89.
  • Zhao C, Deng W, Gage FH. Mechanisms and functional implications of adult neurogenesis. Cell. 2008;132:645–660.
  • Warner‐Schmidt JL, Duman RS. Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment. Hippocampus. 2006;16:239–249. Jan
  • Sahay A, Hen R. Adult hippocampal neurogenesis in depression. Nat Neurosci. 2007;10:1110.
  • Brooker SM, Gobeske KT, Chen J, et al. Hippocampal bone morphogenetic protein signaling mediates behavioral effects of antidepressant treatment. Mol Psychiat. 2017;22:910.
  • Pechnick RN, Zonis S, Wawrowsky K, et al. p21Cip1 restricts neuronal proliferation in the subgranular zone of the dentate gyrus of the hippocampus. Proc Natl Acad Sci USA. 2008;105:1358–1363.
  • Marqués-Torrejón MÁ, Porlan E, Banito A, et al. Cyclin-dependent kinase inhibitor p21 controls adult neural stem cell expansion by regulating Sox2 gene expression. Cell Stem Cell. 2013;12:88–100.
  • Favaro R, Valotta M, Ferri AL, et al. Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh. Nat Neurosci. 2009;12:1248.
  • Ehm O, Göritz C, Covic M, et al. RBPJκ-dependent signaling is essential for long-term maintenance of neural stem cells in the adult hippocampus. J Neurosci. 2010;30:13794–13807.
  • Toda T, Hsu JY, Linker SB, et al. Nup153 interacts with Sox2 to enable bimodal gene regulation and maintenance of neural progenitor cells. Cell Stem Cell. 2017;21:618–634.
  • Li H, Zhong X, Chau KF, et al. Cell cycle-linked MeCP2 phosphorylation modulates adult neurogenesis involving the Notch signalling pathway. Nat Commun. 2014;5:5601.
  • Hsieh J, Zhao X, Genetics epigenetics in a genetics and epigenetics in adult neurogenesis. Cold Spring Harb Perspect Biol. 2016;8:a018911.
  • Jobe EM, Gao Y, Eisinger BE, et al. Methyl-CpG-binding protein MBD1 regulates neuronal lineage commitment through maintaining adult neural stem cell identity. J Neurosci. 2017;37:523–536.
  • Li X, Barkho BZ, Luo Y, et al. Epigenetic regulation of the stem cell mitogen Fgf-2 by Mbd1 in adult neural stem/progenitor cells. J Biol Chem. 2008;283:27644–27652.
  • Winner B, Kohl Z, Gage FH. Neurodegenerative disease and adult neurogenesis. Eur J Neurosci. 2011;33:1139.
  • Chevallier NL, Soriano S, Kang DE, et al. Perturbed neurogenesis in the adult hippocampus associated with presenilin-1 A246E mutation. Am J Pathol. 2005;167:151.
  • Choi SH, Veeraraghavalu K, Lazarov O, et al. Non-cell-autonomous effects of presenilin 1 variants on enrichment-mediated hippocampal progenitor cell proliferation and differentiation. Neuron. 2008;59:568–580.
  • Fuster-Matanzo A, Llorens-Martín M, Hernández F, et al. Role of neuroinflammation in adult neurogenesis and Alzheimer disease: therapeutic approaches. Mediat Inflamm. 2013;2013:1.
  • Smrt RD, Eaves-Egenes J, Barkho BZ, et al. Mecp2 deficiency leads to delayed maturation and altered gene expression in hippocampal neurons. Neurobiol Dis. 2007;27:77–89.
  • Duan X, Chang JH, Ge S, et al. Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain. Cell. 2007;130:1146–1158.
  • Mao Y, Ge X, Frank CL, et al. Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3β/β-catenin signaling. Cell. 2009;136:1017–1031.
  • Kim JY, Duan X, Liu CY, et al. DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212. Neuron. 2009;63:761–773.
  • Gould E, McEwen BS, Tanapat P, et al. Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation. J Neurosci. 1997;17:2492–2498.
  • Murphy T, Dias GP, Thuret S. Effects of diet on brain plasticity in animal and human studies: mind the gap. Neur Plast. 2014;2014:1.
  • Kron MM, Zhang H, Parent JM. The developmental stage of dentate granule cells dictates their contribution to seizure-induced plasticity. J Neurosci. 2010;30:2051–2059.
  • Parent JM, TWY, Leibowitz RT, Geschwind DH, et al. Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci. 1997;17:3727–3738.
  • Ekdahl CT, Claasen JH, Bonde S, et al. Inflammation is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci USA. 2003;100:13632–13637.
  • Arvidsson A, Collin T, Kirik D, et al. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med. 2002;8:963.
  • Tanapat P, Hastings NB, Reeves AJ, et al. Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat. J Neurosci. 1999;19:5792–5801.
  • Cameron HA, Mckay RD. Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus. J Comp Neurol. 2001;435:406–417.
  • Enwere E, Shingo T, Gregg C, et al. Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination. J Neurosci. 2004;24:8354–8365.
  • Rosenzweig MR, Bennett EL. Psychobiology of plasticity: effects of training and experience on brain and behavior. Behav Brain Res. 1996;78:57–65.
  • Nilsson M, Perfilieva E, Johansson U, et al. Enriched environment increases neurogenesis in the adult rat dentate gyrus and improves spatial memory. J Neurobiol. 1999;39:569–578.
  • Brown J, Cooper‐Kuhn CM, et al. Enriched environment and physical activity stimulate hippocampal but not olfactory bulb neurogenesis. Eur J Neurosci. 2003;17:2042–2046.
  • Holmes MM, Galea LA, Mistlberger RE, et al. Adult hippocampal neurogenesis and voluntary running activity: Circadian and dose‐dependent effects. J Neurosci Res. 2004;76:216–222.
  • Duman RS, Malberg J, Nakagawa S. Regulation of adult neurogenesis by psychotropic drugs and stress. J Pharmacol Exp Therap. 2001;299:401–407.
  • Waddell J, Shors TJ. Neurogenesis, learning and associative strength. Eur J Neurosci. 2008;27:3020–3028.
  • Chen H, Pandey GN, Dwivedi Y. Hippocampal cell proliferation regulation by repeated stress and antidepressants. Neuroreport. 2006;17:863–867.
  • Wu X, Castrén E. Co-treatment with diazepam prevents the effects of fluoxetine on the proliferation and survival of hippocampal dentate granule cells. Biol Psychiat. 2009;66:5–8.
  • Chamaa FO, Makkawi AK, Bahmad HF, et al. Nitrous oxide induces prominent cell proliferation in adult rat hippocampal dentate gyrus. Front Cell Neurosci. 2018;12.
  • Eisch AJ, Barrot M, Schad CA, et al. Opiates inhibit neurogenesis in the adult rat hippocampus. Proc Natl Acad Sci USA. 2000;97:7579–7584.
  • Crews FT, Nixon K. Alcohol, neural stem cells, and adult neurogenesis. Alcohol Res Health 2003;27:197–203.
  • Bondolfi L, Ermini F, Long JM, et al. Impact of age and caloric restriction on neurogenesis in the dentate gyrus of C57BL/6 mice. Neurobiol Aging. 2004;25:333–340.
  • Kitamura T, Mishina M, Sugiyama H. Dietary restriction increases hippocampal neurogenesis by molecular mechanisms independent of NMDA receptors. Neurosci Lett. 2006;393:94–96.
  • Nixon K, Crews FT. Binge ethanol exposure decreases neurogenesis in adult rat hippocampus. J Neurochem. 2002;83:1087–1093.
  • Crews F. Inflammasome-IL-1β signaling mediates ethanol inhibition of hippocampal neurogenesis. Front Neurosci. 2012;30:6.
  • Zhang RL, Zhang ZG, Chopp M. Ischemic stroke and neurogenesis in the subventricular zone. Neuropharmacology. 2008;55:345–352.
  • Gould E, Tanapat P, Cameron HA. Adrenal steroids suppress granule cell death in the developing dentate gyrus through an NMDA receptor-dependent mechanism. Dev Brain Res. 1997;103:91–93.
  • Wang W, Pan YW, Wietecha T, et al. Extracellular signal-regulated kinase 5 (ERK5) mediates prolactin-stimulated adult neurogenesis in the subventricular zone and olfactory bulb. J Biol Chem. 2013;288:2623–2631.
  • Choi SH, Bylykbashi E, Chatila ZK, et al. Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model. Science. 2018;361:eaan8821.
  • Altman J. The Neurosciences. Second Study Program. 1967.-
  • McAvoy KM, Scobie KN, Berger S, et al. Modulating neuronal competition dynamics in the dentate gyrus to rejuvenate aging memory circuits. Neuron. 2016;91:1356–1373.
  • Lazarini F, Lledo PM. Is adult neurogenesis essential for olfaction? Trends Neurosci. 2011;34:20–30.
  • Ge S, Sailor KA, Ming GL, et al. Synaptic integration and plasticity of new neurons in the adult hippocampus. J Physiol (Lond). 2008;586:3759–3765.
  • Christian KM, Song H, Ming GL. Functions and dysfunctions of adult hippocampal neurogenesis. Annu Rev Neurosci. 2014;37:243–262.
  • Aimone JB, Deng W, Gage FH. Resolving new memories: a critical look at the dentate gyrus, adult neurogenesis, and pattern separation. Neuron. 2011;70:589–596.
  • Kee N, Teixeira CM, Wang AH, et al. Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus. Nat Neurosci. 2007;10:355.
  • Ramirez-Amaya V, Marrone DF, Gage FH, et al. Integration of new neurons into functional neural networks. J Neurosci. 2006;26:12237–12241.
  • Belnoue L, Grosjean N, Abrous DN, et al. A critical time window for the recruitment of bulbar newborn neurons by olfactory discrimination learning. J Neurosci. 2011;31:1010–1016.
  • Sahay A, Wilson DA, Hen R. Pattern separation: a common function for new neurons in hippocampus and olfactory bulb. Neuron. 2011;70:582–588.
  • Ouzounov DG, Wang T, Wang M, et al. In vivo three-photon imaging of activity of GCaMP6-labeled neurons deep in intact mouse brain. Nat Methods. 2017;14:388.

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