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Brain Structure and Function

, Volume 224, Issue 2, pp 829–846 | Cite as

The α7 nicotinic acetylcholine receptors regulate hippocampal adult-neurogenesis in a sexually dimorphic fashion

  • Simone L. Otto
  • Jerrel L. YakelEmail author
Original Article
  • 192 Downloads

Abstract

Disruption in cholinergic signaling has been linked to many environmental and/or pathological conditions known to modify adult neurogenesis. The α7 nAChRs are in the family of cys-loop receptor channels which have been shown to be neuroprotective in adult neurons and are thought to be critical for survival and integration of immature neurons. However, in developing neurons, poor calcium buffering may cause α7 nAChR activation to be neurotoxic. To investigate whether the α7 nAChR regulates neurogenesis in the hippocampus, we used a combination of mouse genetics and imaging to quantify neural stem cell (NSC) densities located in the dentate gyrus of adult mice. In addition, we considered whether the loss of α7 nAChRs had functional consequences on a spatial discrimination task that is thought to rely on pattern separation mechanisms. We found that the loss of α7 nAChRs resulted in increased neurogenesis in male mice only, while female mice showed increased cell divisions and intermediate progenitors but no change in neurogenesis. Knocking out the α7 nAChR from nestin+ NSCs and their progeny showed signaling in these cells contributes to regulating neurogenesis. In addition, male, but not female, mice lacking α7 nAChRs performed significantly worse in the spatial discrimination task. This task was sexually dimorphic in wild-type mice, but not in the absence of α7 nAChRs. We conclude that α7 nAChRs regulate adult neurogenesis and impact spatial discrimination function in male, but not female mice, via a mechanism involving nestin+ NSCs and their progeny.

Keywords

α7 nicotinic acetylcholine receptors Adult neurogenesis Nestin Pattern separation Spatial discrimination Neural stem cells Sexually dimorphic 

Notes

Acknowledgements

We would like to acknowledge Jesse Cushman for advice on behavior and analysis, and for kindly reviewing the article prior to publication, Patricia Lamb for creation and maintenance of mouse lines, and Charles J. Tucker for assistance with confocal microscopy.

Funding

This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Science.

Compliance with ethical standards

Ethical statement

All procedures were approved and performed in compliance with the NIEHS/NIH Humane Care and Use of Animals Protocols.

Informed consent

This article does not contain any studies with human participants performed by any of the authors. All procedures were approved and performed in compliance with the NIEHS/NIH Humane Care and Use of Animals Protocols.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors. All procedures were approved and performed in compliance with the NIEHS/NIH Humane Care and Use of Animals Protocols.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Adams CE, Yonchek JC, Schulz KM, Graw SL, Stitzel J, Teschke PU, Stevens KE (2012) Reduced Chrna7 expression in mice is associated with decreases in hippocampal markers of inhibitory function: implications for neuropsychiatric diseases. Neuroscience 207:274–282.  https://doi.org/10.1016/j.neuroscience.2012.01.033 CrossRefGoogle Scholar
  2. Aimone JB, Li Y, Lee SW, Clemenson GD, Deng W, Gage FH (2014) Regulation and function of adult neurogenesis: from genes to cognition. Physiol Rev 94:991–1026.  https://doi.org/10.1152/physrev.00004.2014 CrossRefGoogle Scholar
  3. Albuquerque EX, Pereira EF, Alkondon M, Schrattenholz A, Maelicke A (1997) Nicotinic acetylcholine receptors on hippocampal neurons: distribution on the neuronal surface and modulation of receptor activity. J Recept Signal Transduct Res 17:243–266.  https://doi.org/10.3109/10799899709036607 CrossRefGoogle Scholar
  4. Altman J, Das GD (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124:319–335CrossRefGoogle Scholar
  5. Anacker C, Hen R (2017) Adult hippocampal neurogenesis and cognitive flexibility—linking memory and mood. Nat Rev Neurosci 18:335–346.  https://doi.org/10.1038/nrn.2017.45 CrossRefGoogle Scholar
  6. Baier CJ, Pallares ME, Adrover E, Monteleone MC, Brocco MA, Barrantes FJ, Antonelli MC (2015) Prenatal restraint stress decreases the expression of alpha-7 nicotinic receptor in the brain of adult rat offspring. Stress 18:435–445.  https://doi.org/10.3109/10253890.2015.1022148 CrossRefGoogle Scholar
  7. Bao H et al (2017) Long-range GABAergic inputs regulate neural stem cell quiescence and control adult hippocampal neurogenesis. Cell Stem Cell 21:604–617 e605.  https://doi.org/10.1016/j.stem.2017.10.003 CrossRefGoogle Scholar
  8. Bates RC, Stith BJ, Stevens KE, Adams CE (2014) Reduced CHRNA7 expression in C3H mice is associated with increases in hippocampal parvalbumin and glutamate decarboxylase-67 (GAD67) as well as altered levels of GABA(A) receptor subunits. Neuroscience 273:52–64.  https://doi.org/10.1016/j.neuroscience.2014.05.004 CrossRefGoogle Scholar
  9. Belnoue L, Grosjean N, Ladeveze E, Abrous DN, Koehl M (2013) Prenatal stress inhibits hippocampal neurogenesis but spares olfactory bulb neurogenesis. PLoS One 8:e72972.  https://doi.org/10.1371/journal.pone.0072972 CrossRefGoogle Scholar
  10. Besnard A, Sahay A (2016) Adult hippocampal neurogenesis, fear generalization stress. Neuropsychopharmacology 41:24–44.  https://doi.org/10.1038/npp.2015.167 CrossRefGoogle Scholar
  11. Boldrini M et al (2018) Human hippocampal neurogenesis persists throughout aging. Cell Stem Cell 22:589–599 e585.  https://doi.org/10.1016/j.stem.2018.03.015 CrossRefGoogle Scholar
  12. Bonaguidi MA, Song J, Ming GL, Song H (2012) A unifying hypothesis on mammalian neural stem cell properties in the adult hippocampus. Curr Opin Neurobiol 22:754–761.  https://doi.org/10.1016/j.conb.2012.03.013 CrossRefGoogle Scholar
  13. Burket JA, Urbano MR, Deutsch SI (2017) Sugarcoated perineuronal nets regulate “GABAergic” transmission: bittersweet hypothesis in autism spectrum. Disord Clin Neuropharmacol 40:120–130.  https://doi.org/10.1097/WNF.0000000000000209 CrossRefGoogle Scholar
  14. Cabezas C, Irinopoulou T, Cauli B, Poncer JC (2013) Molecular and functional characterization of GAD67-expressing, newborn granule cells in mouse dentate gyrus. Front Neural Circ 7:60.  https://doi.org/10.3389/fncir.2013.00060 Google Scholar
  15. Campbell NR, Fernandes CC, Halff AW, Berg DK (2010) Endogenous signaling through alpha7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampus. J Neurosci 30:8734–8744.  https://doi.org/10.1523/JNEUROSCI.0931-10.2010 CrossRefGoogle Scholar
  16. Chawla MK et al (2005) Sparse, environmentally selective expression of Arc RNA in the upper blade of the rodent fascia dentata by brief spatial experience. Hippocampus 15:579–586.  https://doi.org/10.1002/hipo.20091 CrossRefGoogle Scholar
  17. Clelland CD et al (2009) A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science 325:210–213.  https://doi.org/10.1126/science.1173215 CrossRefGoogle Scholar
  18. Cooper-Kuhn CM, Winkler J, Kuhn HG (2004) Decreased neurogenesis after cholinergic forebrain lesion in the adult rat. J Neurosci Res 77:155–165.  https://doi.org/10.1002/jnr.20116 CrossRefGoogle Scholar
  19. Cushman JD et al (2012) Juvenile neurogenesis makes essential contributions to adult brain structure and plays a sex-dependent role in fear memories. Front Behav Neurosci 6:3.  https://doi.org/10.3389/fnbeh.2012.00003 CrossRefGoogle Scholar
  20. Damborsky JC, Smith KG, Jensen P, Yakel JL (2017) Local cholinergic-GABAergic circuitry within the basal forebrain is modulated by galanin. Brain Struct Funct 222:1385–1400.  https://doi.org/10.1007/s00429-016-1283-0 CrossRefGoogle Scholar
  21. Dannenberg H et al (2015) Synergy of direct and indirect cholinergic septo-hippocampal pathways coordinates firing in hippocampal networks. J Neurosci 35:8394–8410.  https://doi.org/10.1523/JNEUROSCI.4460-14.2015 CrossRefGoogle Scholar
  22. Deisseroth K, Singla S, Toda H, Monje M, Palmer TD, Malenka RC (2004) Excitation-neurogenesis coupling in adult neural stem/progenitor cells. Neuron 42:535–552CrossRefGoogle Scholar
  23. Dickinson-Anson H, Winkler J, Fisher LJ, Song HJ, Poo M, Gage FH (2003) Acetylcholine-secreting cells improve age-induced memory deficits. Mol Ther 8:51–61CrossRefGoogle Scholar
  24. Dineley KT, Pandya AA, Yakel JL (2015) Nicotinic ACh receptors as therapeutic targets in CNS disorders. Trends Pharmacol Sci 36:96–108.  https://doi.org/10.1016/j.tips.2014.12.002 CrossRefGoogle Scholar
  25. Dranovsky A et al (2011) Experience dictates stem cell fate in the adult hippocampus. Neuron 70:908–923.  https://doi.org/10.1016/j.neuron.2011.05.022 CrossRefGoogle Scholar
  26. Encinas JM et al (2011) Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus. Cell Stem Cell 8:566–579.  https://doi.org/10.1016/j.stem.2011.03.010 CrossRefGoogle Scholar
  27. Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH (1998) Neurogenesis in the adult human hippocampus. Nat Med 4:1313–1317.  https://doi.org/10.1038/3305 CrossRefGoogle Scholar
  28. Esposito MS, Piatti VC, Laplagne DA, Morgenstern NA, Ferrari CC, Pitossi FJ, Schinder AF (2005) Neuronal differentiation in the adult hippocampus recapitulates embryonic development. J Neurosci 25:10074–10086.  https://doi.org/10.1523/JNEUROSCI.3114-05.2005 CrossRefGoogle Scholar
  29. Freedman R (2014) alpha7-nicotinic acetylcholine receptor agonists for cognitive enhancement in schizophrenia. Annu Rev Med 65:245–261.  https://doi.org/10.1146/annurev-med-092112-142937 CrossRefGoogle Scholar
  30. Gabor R, Nagle R, Johnson DA, Gibbs RB (2003) Estrogen enhances potassium-stimulated acetylcholine release in the rat hippocampus. Brain Res 962:244–247CrossRefGoogle Scholar
  31. Galea LA (2008) Gonadal hormone modulation of neurogenesis in the dentate gyrus of adult male and female rodents. Brain Res Rev 57:332–341.  https://doi.org/10.1016/j.brainresrev.2007.05.008 CrossRefGoogle Scholar
  32. Gass N et al (2016) An acetylcholine alpha7 positive allosteric modulator rescues a schizophrenia-associated brain endophenotype in the 15q13.3 microdeletion, encompassing CHRNA7. Eur Neuropsychopharmacol 26:1150–1160.  https://doi.org/10.1016/j.euroneuro.2016.03.013 CrossRefGoogle Scholar
  33. Ge S, Yang CH, Hsu KS, Ming GL, Song H (2007) A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain. Neuron 54:559–566.  https://doi.org/10.1016/j.neuron.2007.05.002 CrossRefGoogle Scholar
  34. Gillentine MA, Yin J, Bajic A, Zhang P, Cummock S, Kim JJ, Schaaf CP (2017) Functional consequences of CHRNA7 copy-number alterations in induced pluripotent stem cells and neural progenitor cells. Am J Hum Genet 101:874–887.  https://doi.org/10.1016/j.ajhg.2017.09.024 CrossRefGoogle Scholar
  35. Glenn MJ, Gibson EM, Kirby ED, Mellott TJ, Blusztajn JK, Williams CL (2007) Prenatal choline availability modulates hippocampal neurogenesis and neurogenic responses to enriching experiences in adult female rats. Eur J Neurosci 25:2473–2482.  https://doi.org/10.1111/j.1460-9568.2007.05505.x CrossRefGoogle Scholar
  36. Goncalves JT, Schafer ST, Gage FH (2016) Adult neurogenesis in the hippocampus: from stem. Cells Behav Cell 167:897–914.  https://doi.org/10.1016/j.cell.2016.10.021 Google Scholar
  37. Graham AJ, Martin-Ruiz CM, Teaktong T, Ray MA, Court JA (2002) Human brain nicotinic receptors, their distribution and participation in neuropsychiatric disorders. Curr Drug Targ CNS Neurol Disord 1:387–397CrossRefGoogle Scholar
  38. Gu Z, Yakel JL (2011) Timing-dependent septal cholinergic induction of dynamic hippocampal synaptic plasticity. Neuron 71:155–165.  https://doi.org/10.1016/j.neuron.2011.04.026 CrossRefGoogle Scholar
  39. Guebel DV, Torres NV (2016) Sexual dimorphism and aging in the human hippocampus: identification, validation, and impact of differentially expressed genes by factorial microarray and network analysis. Front Aging Neurosci 8:229.  https://doi.org/10.3389/fnagi.2016.00229 CrossRefGoogle Scholar
  40. Hasselmo ME (2006) The role of acetylcholine in learning and memory. Curr Opin Neurobiol 16:710–715.  https://doi.org/10.1016/j.conb.2006.09.002 CrossRefGoogle Scholar
  41. Hernandez CM, Dineley KT (2012) alpha7 nicotinic acetylcholine receptors in Alzheimer’s disease: neuroprotective, neurotrophic or both? Curr Drug Targ 13:613–622CrossRefGoogle Scholar
  42. Hernandez CM, Kayed R, Zheng H, Sweatt JD, Dineley KT (2010) Loss of alpha7 nicotinic receptors enhances beta-amyloid oligomer accumulation, exacerbating early-stage cognitive decline and septohippocampal pathology in a mouse model of Alzheimer’s disease. J Neurosci 30:2442–2453.  https://doi.org/10.1523/JNEUROSCI.5038-09.2010 CrossRefGoogle Scholar
  43. Hernandez CM et al (2014) Research tool: validation of floxed alpha7 nicotinic acetylcholine receptor conditional knockout mice using in vitro and in vivo approaches. J Physiol 592:3201–3214.  https://doi.org/10.1113/jphysiol.2014.272054 CrossRefGoogle Scholar
  44. Hollands C, Bartolotti N, Lazarov O (2016) Alzheimer’s disease and hippocampal adult neurogenesis exploring shared mechanisms. Front Neurosci 10:178.  https://doi.org/10.3389/fnins.2016.00178 CrossRefGoogle Scholar
  45. Hollands C et al (2017) Depletion of adult neurogenesis exacerbates cognitive deficits in Alzheimer’s disease by compromising hippocampal inhibition. Mol Neurodegener 12:64.  https://doi.org/10.1186/s13024-017-0207-7 CrossRefGoogle Scholar
  46. Holmes MM (2016) Social regulation of adult neurogenesis: a comparative approach. Front Neuroendocrinol 41:59–70.  https://doi.org/10.1016/j.yfrne.2016.02.001 CrossRefGoogle Scholar
  47. Imperato A, Puglisi-Allegra S, Casolini P, Angelucci L (1991) Changes in brain dopamine and acetylcholine release during and following stress are independent of the pituitary-adrenocortical axis. Brain Res 538:111–117CrossRefGoogle Scholar
  48. Jessberger S, Parent JM (2015) Epilepsy and adult neurogenesis. Cold Spring Harb Perspect Biol.  https://doi.org/10.1101/cshperspect.a020677 Google Scholar
  49. Jin K, Peel AL, Mao XO, Xie L, Cottrell BA, Henshall DC, Greenberg DA (2004) Increased hippocampal neurogenesis in Alzheimer’s disease. Proc Natl Acad Sci USA 101:343–347.  https://doi.org/10.1073/pnas.2634794100 CrossRefGoogle Scholar
  50. John D, Shelukhina I, Yanagawa Y, Deuchars J, Henderson Z (2015) Functional alpha7 nicotinic receptors are expressed on immature granule cells of the postnatal dentate gyrus. Brain Res 1601:15–30.  https://doi.org/10.1016/j.brainres.2014.12.041 CrossRefGoogle Scholar
  51. Jones S, Yakel JL (1997) Functional nicotinic ACh receptors on interneurones in the rat hippocampus. J Physiol 504(Pt 3):603–610CrossRefGoogle Scholar
  52. Jung MW, McNaughton BL (1993) Spatial selectivity of unit activity in the hippocampal granular layer. Hippocampus 3:165–182.  https://doi.org/10.1002/hipo.450030209 CrossRefGoogle Scholar
  53. Kang E, Wen Z, Song H, Christian KM, Ming GL (2016) Adult neurogenesis and psychiatric disorders. Cold Spring Harb Perspect Biol.  https://doi.org/10.1101/cshperspect.a019026 Google Scholar
  54. Khiroug SS, Harkness PC, Lamb PW, Sudweeks SN, Khiroug L, Millar NS, Yakel JL (2002) Rat nicotinic ACh receptor alpha7 and beta2 subunits co-assemble to form functional heteromeric nicotinic receptor channels. J Physiol 540:425–434CrossRefGoogle Scholar
  55. King JR, Gillevet TC, Kabbani N (2017) A G protein-coupled alpha7 nicotinic receptor regulates signaling and TNF-alpha release in microglia. FEBS Open Biol 7:1350–1361.  https://doi.org/10.1002/2211-5463.12270 CrossRefGoogle Scholar
  56. Kita Y, Ago Y, Higashino K, Asada K, Takano E, Takuma K, Matsuda T (2014) Galantamine promotes adult hippocampal neurogenesis via M(1) muscarinic and alpha7 nicotinic receptors in mice. Int J Neuropsychopharmacol 17:1957–1968.  https://doi.org/10.1017/S1461145714000613 CrossRefGoogle Scholar
  57. Kotani S, Yamauchi T, Teramoto T, Ogura H (2006) Pharmacological evidence of cholinergic involvement in adult hippocampal neurogenesis in rats. Neuroscience 142:505–514.  https://doi.org/10.1016/j.neuroscience.2006.06.035 CrossRefGoogle Scholar
  58. Lagace DC et al (2007) Dynamic contribution of nestin-expressing stem cells to adult neurogenesis. J Neurosci 27:12623–12629.  https://doi.org/10.1523/JNEUROSCI.3812-07.2007 CrossRefGoogle Scholar
  59. Lazarov O, Marr RA (2010) Neurogenesis and Alzheimer’s disease: at the crossroads. Exp Neurol 223:267–281.  https://doi.org/10.1016/j.expneurol.2009.08.009 CrossRefGoogle Scholar
  60. Lederle L et al (2011) Reward-related behavioral paradigms for addiction research in the mouse: performance of common inbred strains. PLoS One 6:e15536.  https://doi.org/10.1371/journal.pone.0015536 CrossRefGoogle Scholar
  61. Levin ED (2012) alpha7-Nicotinic receptors and cognition. Curr Drug Targ 13:602–606CrossRefGoogle Scholar
  62. Lewis AS, Pittenger ST, Mineur YS, Stout D, Smith PH, Picciotto MR (2017) Bidirectional regulation of aggression in mice by hippocampal alpha-7 nicotinic acetylcholine receptors. Neuropsychopharmacology.  https://doi.org/10.1038/npp.2017.276 Google Scholar
  63. Luine V, Gomez J, Beck K, Bowman R (2017) Sex differences in chronic stress effects on cognition in rodents. Pharmacol Biochem Behav 152:13–19.  https://doi.org/10.1016/j.pbb.2016.08.005 CrossRefGoogle Scholar
  64. Lykhmus O et al (2015) alpha7 Nicotinic acetylcholine receptor-specific antibody induces inflammation and amyloid beta42 accumulation in the mouse brain to impair memory. PLoS One 10:e0122706.  https://doi.org/10.1371/journal.pone.0122706 CrossRefGoogle Scholar
  65. Martin LF, Freedman R (2007) Schizophrenia and the alpha7 nicotinic acetylcholine receptor. Int Rev Neurobiol 78:225–246.  https://doi.org/10.1016/S0074-7742(06)78008-4 CrossRefGoogle Scholar
  66. Martinez-Pinilla E, Ordonez C, Del Valle E, Navarro A, Tolivia J (2016) Regional and gender study of neuronal density in brain during aging and in Alzheimer’s disease. Front Aging Neurosci 8:213.  https://doi.org/10.3389/fnagi.2016.00213 CrossRefGoogle Scholar
  67. Mechawar N et al (2004) Nicotinic receptors regulate the survival of newborn neurons in the adult olfactory bulb. Proc Natl Acad Sci USA 101:9822–9826.  https://doi.org/10.1073/pnas.0403361101 CrossRefGoogle Scholar
  68. Orr-Urtreger A, Broide RS, Kasten MR, Dang H, Dani JA, Beaudet AL, Patrick JW (2000) Mice homozygous for the L250T mutation in the alpha7 nicotinic acetylcholine receptor show increased neuronal apoptosis and die within 1 day of birth. J Neurochem 74:2154–2166CrossRefGoogle Scholar
  69. Paez-Gonzalez P, Asrican B, Rodriguez E, Kuo CT (2014) Identification of distinct ChAT(+) neurons and activity-dependent control of postnatal SVZ neurogenesis. Nat Neurosci 17:934–942.  https://doi.org/10.1038/nn.3734 CrossRefGoogle Scholar
  70. Pan YW, Chan GC, Kuo CT, Storm DR, 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 32:6444–6455.  https://doi.org/10.1523/JNEUROSCI.6076-11.2012 CrossRefGoogle Scholar
  71. Papouin T, Dunphy JM, Tolman M, Dineley KT, Haydon PG (2017) Septal cholinergic neuromodulation tunes the astrocyte-dependent gating of hippocampal NMDA receptors to wakefulness. Neuron 94:840–854 e847.  https://doi.org/10.1016/j.neuron.2017.04.021 CrossRefGoogle Scholar
  72. Plitman E et al (2017) Kynurenic acid in schizophrenia: a systematic review and meta-analysis. Schizophr Bull 43:764–777.  https://doi.org/10.1093/schbul/sbw221 CrossRefGoogle Scholar
  73. Rubboli F, Court JA, Sala C, Morris C, Chini B, Perry E, Clementi F (1994) Distribution of nicotinic receptors in the human hippocampus and thalamus. Eur J Neurosci 6:1596–1604CrossRefGoogle Scholar
  74. Sahay A et al (2011) Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature 472:466–470.  https://doi.org/10.1038/nature09817 CrossRefGoogle Scholar
  75. Santoro A (2013) Reassessing pattern separation in the dentate gyrus. Front Behav Neurosci 7:96.  https://doi.org/10.3389/fnbeh.2013.00096 CrossRefGoogle Scholar
  76. Schmidt-Hieber C, Jonas P, Bischofberger J (2004) Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature 429:184–187.  https://doi.org/10.1038/nature02553 CrossRefGoogle Scholar
  77. Sharma G, Vijayaraghavan S (2001) Nicotinic cholinergic signaling in hippocampal astrocytes involves calcium-induced calcium release from intracellular stores. Proc Natl Acad Sci USA 98:4148–4153.  https://doi.org/10.1073/pnas.071540198 CrossRefGoogle Scholar
  78. Shen JX, Yakel JL (2012) Functional alpha7 nicotinic ACh receptors on astrocytes in rat hippocampal CA1 slices. J Mol Neurosci 48:14–21.  https://doi.org/10.1007/s12031-012-9719-3 CrossRefGoogle Scholar
  79. Shytle RD et al (2004) Cholinergic modulation of microglial activation by alpha 7 nicotinic receptors. J Neurochem 89:337–343.  https://doi.org/10.1046/j.1471-4159.2004.02347.x CrossRefGoogle Scholar
  80. Song J et al (2012) Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision. Nature 489:150–154.  https://doi.org/10.1038/nature11306 CrossRefGoogle Scholar
  81. Song J et al (2013) Parvalbumin interneurons mediate neuronal circuitry-neurogenesis coupling in the adult hippocampus. Nat Neurosci 16:1728–1730.  https://doi.org/10.1038/nn.3572 CrossRefGoogle Scholar
  82. Sorrells SF et al (2018) Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature 555:377–381.  https://doi.org/10.1038/nature25975 CrossRefGoogle Scholar
  83. Spalding KL et al (2013) Dynamics of hippocampal neurogenesis in adult humans. Cell 153:1219–1227.  https://doi.org/10.1016/j.cell.2013.05.002 CrossRefGoogle Scholar
  84. Spencer JL, Waters EM, Romeo RD, Wood GE, Milner TA, McEwen BS (2008) Uncovering the mechanisms of estrogen effects on hippocampal function. Front Neuroendocrinol 29:219–237.  https://doi.org/10.1016/j.yfrne.2007.08.006 CrossRefGoogle Scholar
  85. Tanapat P, Hastings NB, Reeves AJ, Gould E (1999) Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat. J Neurosci 19:5792–5801CrossRefGoogle Scholar
  86. Tashiro A, Sandler VM, Toni N, Zhao C, Gage FH (2006) NMDA-receptor-mediated, cell-specific integration of new neurons in adult dentate gyrus. Nature 442:929–933.  https://doi.org/10.1038/nature05028 CrossRefGoogle Scholar
  87. Teaktong T et al (2003) Alzheimer’s disease is associated with a selective increase in alpha7 nicotinic acetylcholine receptor immunoreactivity in astrocytes. Glia 41:207–211.  https://doi.org/10.1002/glia.10132 CrossRefGoogle Scholar
  88. van Praag H, Kempermann G, Gage FH (1999) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2:266–270.  https://doi.org/10.1038/6368 CrossRefGoogle Scholar
  89. Velazquez R et al (2013) Maternal choline supplementation improves spatial learning and adult hippocampal neurogenesis in the Ts65Dn mouse model of Down syndrome. Neurobiol Dis 58:92–101.  https://doi.org/10.1016/j.nbd.2013.04.016 CrossRefGoogle Scholar
  90. Voytenko LP et al (2015) Hippocampal GABAergic interneurons coexpressing alpha7-nicotinic receptors and connexin-36 are able to improve neuronal viability under oxygen-glucose deprivation. Brain Res 1616:134–145.  https://doi.org/10.1016/j.brainres.2015.04.061 CrossRefGoogle Scholar
  91. Wu J, Liu Q, Tang P, Mikkelsen JD, Shen J, Whiteaker P, Yakel JL (2016) Heteromeric alpha7beta2 nicotinic acetylcholine receptors in the brain. Trends Pharmacol Sci 37:562–574.  https://doi.org/10.1016/j.tips.2016.03.005 CrossRefGoogle Scholar
  92. Yu Y et al (2009) Increased hippocampal neurogenesis in the progressive stage of Alzheimer’s disease phenotype in an APP/PS1 double transgenic mouse model. Hippocampus 19:1247–1253.  https://doi.org/10.1002/hipo.20587 CrossRefGoogle Scholar
  93. Yuan M et al (2017) Somatostatin-positive interneurons in the dentate gyrus of mice provide local- and long-range septal synaptic inhibition. Elife.  https://doi.org/10.7554/eLife.21105 Google Scholar

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Authors and Affiliations

  1. 1.Neurobiology LaboratoryNational Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human ServicesResearch Triangle ParkUSA

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