Frontiers in Biology

, Volume 8, Issue 5, pp 496–507 | Cite as

Novel functions of GABA signaling in adult neurogenesis

  • Adalto Pontes
  • Yonggang Zhang
  • Wenhui Hu


Neurotransmitter gamma-aminobutiric acid (GABA) through ionotropic GABAA and metabotropic GABAB receptors plays key roles in modulating the development, plasticity and function of neuronal networks. GABA is inhibitory in mature neurons but excitatory in immature neurons, neuroblasts and neural stem/progenitor cells (NSCs/NPCs). The switch from excitatory to inhibitory occurs following the development of glutamatergic synaptic input and results from the dynamic changes in the expression of Na+/K+/2Cl co-transporter NKCC1 driving Cl influx and neuron-specific K+/Cl co-transporter KCC2 driving Cl efflux. The developmental transition of KCC2 expression is regulated by Disrupted-in-Schizophrenia 1 (DISC1) and brain-derived neurotrophic factor (BDNF) signaling. The excitatory GABA signaling during early neurogenesis is important to the activity/experience-induced regulation of NSC quiescence, NPC proliferation, neuroblast migration and new-born neuronal maturation/functional integration. The inhibitory GABA signaling allows for the sparse and static functional networking essential for learning/memory development and maintenance.


neurogenesis neural stem cells GABA signal pathways co-transporter neurons 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Achilles K, Okabe A, Ikeda M, Shimizu-Okabe C, Yamada J, Fukuda A, Luhmann H J, Kilb W (2007). Kinetic properties of Cl uptake mediated by Na+-dependent K+-2Cl cotransport in immature rat neocortical neurons. J Neurosci, 27(32): 8616–8627PubMedGoogle Scholar
  2. Aguado F, Carmona M A, Pozas E, Aguiló A, MartÍnez-Guijarro F J, Alcantara S, Borrell V, Yuste R, Ibañez C F, Soriano E (2003). BDNF regulates spontaneous correlated activity at early developmental stages by increasing synaptogenesis and expression of the K+/Cl cotransporter KCC2. Development, 130(7): 1267–1280PubMedGoogle Scholar
  3. 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
  4. Altman J, Das G D (1966). Autoradiographic and histological studies of postnatal neurogenesis. I. A longitudinal investigation of the kinetics, migration and transformation of cells incorporating tritiated thymidine in neonate rats, with special reference to postnatal neurogenesis in some brain regions. J Comp Neurol, 126(3): 337–389PubMedGoogle Scholar
  5. Andäng M, Hjerling-Leffler J, Moliner A, Lundgren T K, Castelo-Branco G, Nanou E, Pozas E, Bryja V, Halliez S, Nishimaru H, Wilbertz J, Arenas E, Koltzenburg M, Charnay P, El Manira A, Ibañez C F, Ernfors P (2008). Histone H2AX-dependent GABA(A) receptor regulation of stem cell proliferation. Nature, 451(7177): 460–464PubMedGoogle Scholar
  6. Becker L, Peterson J, Kulkarni S, Pasricha P J (2013). Ex vivo neurogenesis within enteric ganglia occurs in a PTEN dependent manner. PLoS ONE, 8(3): e59452PubMedGoogle Scholar
  7. Benarroch E E (2013). Cation-chloride cotransporters in the nervous system: general features and clinical correlations. Neurology, 80(8): 756–763PubMedGoogle Scholar
  8. Binder S, Baier P C, Mölle M, Inostroza M, Born J, Marshall L (2012). Sleep enhances memory consolidation in the hippocampusdependent object-place recognition task in rats. Neurobiol Learn Mem, 97(2): 213–219PubMedGoogle Scholar
  9. Bowery N G, Hill D R, Hudson A L, Doble A, Middlemiss D N, Shaw J, Turnbull M (1980). (-)Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor. Nature, 283(5742): 92–94PubMedGoogle Scholar
  10. Chamma I, Chevy Q, Poncer J C, Lévi S (2012). Role of the neuronal KCl co-transporter KCC2 in inhibitory and excitatory neurotransmission. Front Cell Neurosci, 6: 5PubMedGoogle Scholar
  11. Chater T E, Goda Y (2013). CA3 mossy fiber connections: giant synapses that gain control. Neuron, 77(1): 4–6PubMedGoogle Scholar
  12. Cherubini E, Griguoli M, Safiulina V, Lagostena L (2011). The depolarizing action of GABA controls early network activity in the developing hippocampus. Mol Neurobiol, 43(2): 97–106PubMedGoogle Scholar
  13. Clelland C D, Choi M, Romberg C, Clemenson G D Jr, Fragniere A, Tyers P, Jessberger S, Saksida L M, Barker R A, Gage F H, Bussey T J (2009). A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science, 325(5937): 210–213PubMedGoogle Scholar
  14. Cohen E, Ivenshitz M, Amor-Baroukh V, Greenberger V, Segal M (2008). Determinants of spontaneous activity in networks of cultured hippocampus. Brain Res, 1235: 21–30PubMedGoogle Scholar
  15. Cortes C, Galindo F, Galicia S, Cebada J, Flores A (2013). Excitatory actions of GABA in developing chick vestibular afferents: Effects on resting electrical activity. Synapse, 67(7): 374–381PubMedGoogle Scholar
  16. Couillard-Després S (2013). Hippocampal neurogenesis and ageing. Curr Top Behav Neurosci, 15: 343–355PubMedGoogle Scholar
  17. Couillard-Despres S, Iglseder B, Aigner L (2011). Neurogenesis, cellular plasticity and cognition: the impact of stem cells in the adult and aging brain-a mini-review. Gerontology, 57(6): 559–564PubMedGoogle Scholar
  18. Cryan J F, Slattery D A (2010). GABAB receptors and depression. Current status. Adv Pharmacol, 58: 427–451Google Scholar
  19. Cserép C, Szabadits E, Szőnyi A, Watanabe M, Freund T F, Nyiri G (2012). NMDA receptors in GABAergic synapses during postnatal development. PLoS ONE, 7(5): e37753PubMedGoogle Scholar
  20. Curtis M A, Low V F, Faull R L (2012). Neurogenesis and progenitor cells in the adult human brain: a comparison between hippocampal and subventricular progenitor proliferation. Dev Neurobiol, 72(7): 990–1005PubMedGoogle Scholar
  21. Daynac M, Chicheportiche A, Pineda J R, Gauthier L R, Boussin F D, Mouthon M A (2013). Quiescent neural stem cells exit dormancy upon alteration of GABAAR signaling following radiation damage. Stem Cell Res (Amst), 11(1): 516–528Google Scholar
  22. Delpire E (2000). Cation-chloride cotransporters in neuronal communication. News Physiol Sci, 15: 309–312PubMedGoogle Scholar
  23. Dieni C V, Chancey J H, Overstreet-Wadiche L S (2012). Dynamic functions of GABA signaling during granule cell maturation. Front Neural Circuits, 6: 113PubMedGoogle Scholar
  24. Duan X, Chang J H, Ge S, Faulkner R L, Kim J Y, Kitabatake Y, Liu X B, Yang C H, Jordan J D, Ma D K, Liu C Y, Ganesan S, Cheng H J, Ming G L, Lu B, Song H (2007). Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain. Cell, 130(6): 1146–1158PubMedGoogle Scholar
  25. Dzhala V I, Talos D M, Sdrulla D A, Brumback A C, Mathews G C, Benke T A, Delpire E, Jensen F E, Staley K J (2005). NKCC1 transporter facilitates seizures in the developing brain. Nat Med, 11(11): 1205–1213PubMedGoogle Scholar
  26. Eisch A J, Petrik D (2012). Depression and hippocampal neurogenesis: a road to remission? Science, 338(6103): 72–75PubMedGoogle Scholar
  27. Erlander M G, Tillakaratne N J, Feldblum S, Patel N, Tobin A J (1991). Two genes encode distinct glutamate decarboxylases. Neuron, 7(1): 91–100PubMedGoogle Scholar
  28. Espinosa J, Rocha A, Nunes F, Costa M S, Schein V, Kazlauckas V, Kalinine E, Souza D O, Cunha R A, Porciúncula L O (2013). Caffeine consumption prevents memory impairment, neuronal damage, and adenosine A2A receptors upregulation in the hippocampus of a rat model of sporadic dementia. J Alzheimers Dis, 34(2): 509–518PubMedGoogle Scholar
  29. Faigle R, Song H (2013). Signaling mechanisms regulating adult neural stem cells and neurogenesis. Biochim Biophys Acta, 1830(2): 2435–2448PubMedGoogle Scholar
  30. Feierstein C E (2012). Linking adult olfactory neurogenesis to social behavior. Front Neurosci, 6: 173PubMedGoogle Scholar
  31. Feierstein C E, Lazarini F, Wagner S, Gabellec M M, de Chaumont F, Olivo-Marin J C, Boussin F D, Lledo P M, Gheusi G (2010). Disruption of adult neurogenesis in the olfactory bulb affects social interaction but not maternal behavior. Front Behav Neurosci, 4: 176PubMedGoogle Scholar
  32. Fernandes F S, de Souza A S, do Carmo M, Boaventura G T (2011). Maternal intake of flaxseed-based diet (Linum usitatissimum) on hippocampus fatty acid profile: implications for growth, locomotor activity and spatial memory. Nutrition, 27(10): 1040–1047PubMedGoogle Scholar
  33. Fernando R N, Eleuteri B, Abdelhady S, Nussenzweig A, Andäng M, Ernfors P (2011). Cell cycle restriction by histone H2AX limits proliferation of adult neural stem cells. Proc Natl Acad Sci USA, 108(14): 5837–5842PubMedGoogle Scholar
  34. Fiumelli H, Woodin M A (2007). Role of activity-dependent regulation of neuronal chloride homeostasis in development. Curr Opin Neurobiol, 17(1): 81–86PubMedGoogle Scholar
  35. Foster P P, Rosenblatt K P, Kuljiš R O (2011). Exercise-induced cognitive plasticity, implications for mild cognitive impairment and Alzheimer’s disease. Front Neurol, 2: 28PubMedGoogle Scholar
  36. Fotuhi M, Do D, Jack C (2012). Modifiable factors that alter the size of the hippocampus with ageing. Nat Rev Neurol, 8(4): 189–202PubMedGoogle Scholar
  37. GarcÍa-Verdugo J M, Ferrón S, Flames N, Collado L, Desfilis E, Font E (2002). The proliferative ventricular zone in adult vertebrates: a comparative study using reptiles, birds, and mammals. Brain Res Bull, 57(6): 765–775PubMedGoogle Scholar
  38. Garrett L, Lie D C, Hrabé de Angelis M, Wurst W, Hölter S M (2012). Voluntary wheel running in mice increases the rate of neurogenesis without affecting anxiety-related behaviour in single tests. BMC Neurosci, 13(1): 61PubMedGoogle Scholar
  39. Gershon M D (2011). Behind an enteric neuron there may lie a glial cell. J Clin Invest, 121(9): 3386–3389PubMedGoogle Scholar
  40. Glasper E R, Gould E (2013). Sexual experience restores age-related decline in adult neurogenesis and hippocampal function. Hippocampus: n/a Gonzalez-Perez O (2012). Neural stem cells in the adult human brain. Biol Biomed Rep, 2(1): 59–69Google Scholar
  41. Goto K, Kato G, Kawahara I, Luo Y, Obata K, Misawa H, Ishikawa T, Kuniyasu H, Nabekura J, Takaki M (2013). In vivo imaging of enteric neurogenesis in the deep tissue of mouse small intestine. PLoS ONE, 8(1): e54814PubMedGoogle Scholar
  42. Haan N, Goodman T, Najdi-Samiei A, Stratford CM, Rice R, El Agha E, Bellusci S, Hajihosseini MK (2013). Fgf10-expressing tanycytes add new neurons to the appetite/energy-balance regulating centers of the postnatal and adult hypothalamus. J Neurosci, 33(14): 6170–6180PubMedGoogle Scholar
  43. Huang Y, Wang J J, Yung W H (2013). Coupling Between GABA-A Receptor and Chloride Transporter Underlies Ionic Plasticity in Cerebellar Purkinje Neurons. Cerebellum, 12(3): 328–330PubMedGoogle Scholar
  44. Huehnchen P, Prozorovski T, Klaissle P, Lesemann A, Ingwersen J, Wolf S A, Kupsch A, Aktas O, Steiner B (2011). Modulation of adult hippocampal neurogenesis during myelin-directed autoimmune neuroinflammation. Glia, 59(1): 132–142PubMedGoogle Scholar
  45. Imayoshi I, Sakamoto M, Ohtsuka T, Kageyama R (2009). Continuous neurogenesis in the adult brain. Dev Growth Differ, 51(3): 379–386PubMedGoogle Scholar
  46. Ivakine E A, Acton B A, Mahadevan V, Ormond J, Tang M, Pressey J C, Huang M Y, Ng D, Delpire E, Salter M W, Woodin M A, McInnes R R (2013). Neto2 is a KCC2 interacting protein required for neuronal Cl-regulation in hippocampal neurons. Proc Natl Acad Sci USA, 110(9): 3561–3566PubMedGoogle Scholar
  47. Joseph NM, He S, Quintana E, Kim Y G, Núñez G, Morrison S J (2011). Enteric glia are multipotent in culture but primarily form glia in the adult rodent gut. J Clin Invest, 121(9): 3398–3411PubMedGoogle Scholar
  48. Jun H, Mohammed Qasim Hussaini S, Rigby M J, Jang M H (2012). Functional role of adult hippocampal neurogenesis as a therapeutic strategy for mental disorders. Neural Plast, 2012: 854285PubMedGoogle Scholar
  49. Kanaka C, Ohno K, Okabe A, Kuriyama K, Itoh T, Fukuda A, Sato K (2001). The differential expression patterns of messenger RNAs encoding K-Cl cotransporters (KCC1,2) and Na-K-2Cl cotransporter (NKCC1) in the rat nervous system. Neuroscience, 104(4): 933–946PubMedGoogle Scholar
  50. Keller M, Douhard Q, Baum M J, Bakker J (2006). Destruction of the main olfactory epithelium reduces female sexual behavior and olfactory investigation in female mice. Chem Senses, 31(4): 315–323PubMedGoogle Scholar
  51. Kempermann G (2011). Neurogenesis in the hippocampus. In: Adult neurogenesis 2:Stem cells and neuronal development in the adult brain. Oxford University Press, New YorkGoogle Scholar
  52. Khazipov R, Esclapez M, Caillard O, Bernard C, Khalilov I, Tyzio R, Hirsch J, Dzhala V, Berger B, Ben-Ari Y (2001). Early development of neuronal activity in the primate hippocampus in utero. J Neurosci, 21(24): 9770–9781PubMedGoogle Scholar
  53. Kim J Y, Liu C Y, Zhang F, Duan X, Wen Z, Song J, Feighery E, Lu B, Rujescu D, St Clair D, Christian K, Callicott J H, Weinberger D R, Song H, Ming G L (2012). Interplay between DISC1 and GABA signaling regulates neurogenesis in mice and risk for schizophrenia. Cell, 148(5): 1051–1064PubMedGoogle Scholar
  54. Laranjeira C, Sandgren K, Kessaris N, Richardson W, Potocnik A, Vanden Berghe P, Pachnis V (2011). Glial cells in the mouse enteric nervous system can undergo neurogenesis in response to injury. J Clin Invest, 121(9): 3412–3424PubMedGoogle Scholar
  55. Lee C, Hu J, Ralls S, Kitamura T, Loh Y P, Yang Y, Mukouyama Y S, Ahn S (2012). The molecular profiles of neural stem cell niche in the adult subventricular zone. PLoS ONE, 7(11): e50501PubMedGoogle Scholar
  56. Lee D A, Blackshaw S (2012). Functional implications of hypothalamic neurogenesis in the adult mammalian brain. Int J Dev Neurosci, 30(8): 615–621PubMedGoogle Scholar
  57. Lee M C, Inoue K, Okamoto M, Liu Y F, Matsui T, Yook J S, Soya H (2013). Voluntary resistance running induces increased hippocampal neurogenesis in rats comparable to load-free running. Neurosci Lett, 537: 6–10PubMedGoogle Scholar
  58. Li J, Tang Y, Cai D (2012). IKKβ/NF-κB disrupts adult hypothalamic neural stem cells to mediate a neurodegenerative mechanism of dietary obesity and pre-diabetes. Nat Cell Biol, 14(10): 999–1012PubMedGoogle Scholar
  59. Lin D Y, Zhang S Z, Block E, Katz L C (2005). Encoding social signals in the mouse main olfactory bulb. Nature, 434(7032): 470–477PubMedGoogle Scholar
  60. Liu X, Wang Q, Haydar T F, Bordey A (2005). Nonsynaptic GABA signaling in postnatal subventricular zone controls proliferation of GFAP-expressing progenitors. Nat Neurosci, 8(9): 1179–1187PubMedGoogle Scholar
  61. Lovatel G A, Elsner V R, Bertoldi K, Vanzella C, Moysés F S, Vizuete A, Spindler C, Cechinel L R, Netto C A, Muotri A R, Siqueira I R (2013). Treadmill exercise induces age-related changes in aversive memory, neuroinflammatory and epigenetic processes in the rat hippocampus. Neurobiol Learn Mem, 101: 94–102PubMedGoogle Scholar
  62. Ludwig A, Uvarov P, Pellegrino C, Thomas-Crusells J, Schuchmann S, Saarma M, Airaksinen M S, Rivera C (2011a). Neurturin evokes MAPK-dependent upregulation of Egr4 and KCC2 in developing neurons. Neural Plast, 2011: 1–8PubMedGoogle Scholar
  63. Ludwig A, Uvarov P, Soni S, Thomas-Crusells J, Airaksinen M S, Rivera C (2011b). Early growth response 4 mediates BDNF induction of potassium chloride cotransporter 2 transcription. J Neurosci, 31(2): 644–649PubMedGoogle Scholar
  64. Mak G K, Weiss S (2010). Paternal recognition of adult offspring mediated by newly generated CNS neurons. Nat Neurosci, 13(6): 753–758PubMedGoogle Scholar
  65. Mao Y, Ge X, Frank C L, Madison J M, Koehler A N, Doud M K, Tassa C, Berry E M, Soda T, Singh K K, Biechele T, Petryshen T L, Moon R T, Haggarty S J, Tsai L H (2009). Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3β/β-catenin signaling. Cell, 136(6): 1017–103PubMedGoogle Scholar
  66. Markwardt S J, Wadiche J I, Overstreet-Wadiche L S (2009). Inputspecific GABAergic signaling to newborn neurons in adult dentate gyrus. J Neurosci, 29(48): 15063–15072PubMedGoogle Scholar
  67. McDermott K W, Lantos P L (1990). Cell proliferation in the subependymal layer of the postnatal marmoset, Callithrix jacchus. Brain Res Dev Brain Res, 57(2): 269–277PubMedGoogle Scholar
  68. McEown K, Treit D (2010). Inactivation of the dorsal or ventral hippocampus with muscimol differentially affects fear and memory. Brain Res, 1353: 145–151PubMedGoogle Scholar
  69. McNay D E, Briançon N, Kokoeva M V, Maratos-Flier E, Flier J S (2012). Remodeling of the arcuate nucleus energy-balance circuit is inhibited in obese mice. J Clin Invest, 122(1): 142–152PubMedGoogle Scholar
  70. Metzger M (2010). Neurogenesis in the enteric nervous system. Arch Ital Biol, 148(2): 73–83PubMedGoogle Scholar
  71. Ming G L, Song H (2009). DISC1 partners with GSK3beta in neurogenesis. Cell, 136(6): 990–992PubMedGoogle Scholar
  72. Misane I, Kruis A, Pieneman A W, Ögren S O, Stiedl O (2013). GABA (A) receptor activation in the CA1 area of the dorsal hippocampus impairs consolidation of conditioned contextual fear in C57BL/6J mice. Behav Brain Res, 238: 160–169PubMedGoogle Scholar
  73. Moss J, Toni N (2013). A circuit-based gatekeeper for adult neural stem cell proliferation: Parvalbumin-expressing interneurons of the dentate gyrus control the activation and proliferation of quiescent adult neural stem cells. Bioessays, 35(1): 28–33PubMedGoogle Scholar
  74. Mu Y, Gage F H (2011). Adult hippocampal neurogenesis and its role in Alzheimer’s disease. Mol Neurodegener, 6(1): 85PubMedGoogle Scholar
  75. 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): 188–201PubMedGoogle Scholar
  76. 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: 1253PubMedGoogle Scholar
  77. Owens D F, Kriegstein A R (2002). Is there more to GABA than synaptic inhibition? Nat Rev Neurosci, 3(9): 715–727PubMedGoogle Scholar
  78. Pavlov I, Riekki R, Taira T (2004). Synergistic action of GABA-A and NMDA receptors in the induction of long-term depression in glutamatergic synapses in the newborn rat hippocampus. Eur J Neurosci, 20(11): 3019–3026PubMedGoogle Scholar
  79. Pearce J M (2001). Ammon’s horn and the hippocampus. J Neurol Neurosurg Psychiatry, 71(3): 351PubMedGoogle Scholar
  80. Penfield W, Milner B (1958). Memory deficit produced by bilateral lesions in the hippocampal zone. AMA Arch Neurol Psychiatry, 79(5): 475–497PubMedGoogle Scholar
  81. Pierce A A, Xu A W (2010). De novo neurogenesis in adult hypothalamus as a compensatory mechanism to regulate energy balance. J Neurosci, 30(2): 723–730PubMedGoogle Scholar
  82. Platel J C, Dave K A, Bordey A (2008). Control of neuroblast production and migration by converging GABA and glutamate signals in the postnatal forebrain. J Physiol, 586(16): 3739–3743PubMedGoogle Scholar
  83. Platel J C, Stamboulian S, Nguyen I, Bordey A (2010). Neurotransmitter signaling in postnatal neurogenesis: The first leg. Brain Res Brain Res Rev, 63(1–2): 60–71Google Scholar
  84. Raimondo J V, Markram H, Akerman C J (2012). Short-term ionic plasticity at GABAergic synapses. Front Synaptic Neurosci, 4: 5PubMedGoogle Scholar
  85. Recinto P, Samant A R, Chavez G, Kim A, Yuan C J, Soleiman M, Grant Y, Edwards S, Wee S, Koob G F, George O, Mandyam C D (2012). Levels of neural progenitors in the hippocampus predict memory impairment and relapse to drug seeking as a function of excessive methamphetamine self-administration. Neuropsychopharmacology, 37(5): 1275–1287PubMedGoogle Scholar
  86. Reif A, Fritzen S, Finger M, Strobel A, Lauer M, Schmitt A, Lesch K P (2006). Neural stem cell proliferation is decreased in schizophrenia, but not in depression. Mol Psychiatry, 11(5): 514–522PubMedGoogle Scholar
  87. Rinehart J, Vázquez N, Kahle K T, Hodson C A, Ring A M, Gulcicek E E, Louvi A, Bobadilla N A, Gamba G, Lifton R P (2011). WNK2 kinase is a novel regulator of essential neuronal cation-chloride cotransporters. J Biol Chem, 286(34): 30171–30180PubMedGoogle Scholar
  88. Rivera C, Li H, Thomas-Crusells J, Lahtinen H, Viitanen T, Nanobashvili A, Kokaia Z, Airaksinen M S, Voipio J, Kaila K, Saarma M (2002). BDNF-induced TrkB activation down-regulates the K+- Cl- cotransporter KCC2 and impairs neuronal Cl- extrusion. J Cell Biol, 159(5): 747–752PubMedGoogle Scholar
  89. Ruiz A J, Kullmann D M (2012). Ionotropic receptors at hippocampal mossy fibers: roles in axonal excitability, synaptic transmission, and plasticity. Front Neural Circuits, 6: 112PubMedGoogle Scholar
  90. Saffrey M J (2013). Cellular changes in the enteric nervous system during ageing. Dev BiolGoogle Scholar
  91. 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): 466–470PubMedGoogle Scholar
  92. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R (2003). Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science, 301(5634): 805–809PubMedGoogle Scholar
  93. Saxe M D, Battaglia F, Wang JW, Malleret G, David D J, Monckton J E, Garcia A D, Sofroniew M V, Kandel E R, Santarelli L, Hen R, Drew M R (2006). Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. Proc Natl Acad Sci USA, 103(46): 17501–17506PubMedGoogle Scholar
  94. Scoville W B, Milner B (1957). Loss of recent memory after bilateral hippocampal lesions. J Neurol Neurosurg Psychiatry, 20(1): 11–21PubMedGoogle Scholar
  95. Scullin C S, Partridge L D (2012). Modulation by pregnenolone sulfate of filtering properties in the hippocampal trisynaptic circuit. Hippocampus, 22(11): 2184–2198PubMedGoogle Scholar
  96. Sheridan G K, Pickering M, Twomey C, Moynagh P N, O’Connor J J, Murphy K J (2007). NF-κB activity in distinct neural subtypes of the rat hippocampus: Influence of time and GABA antagonism in acute slice preparations. Learn Mem, 14(8): 525–532PubMedGoogle Scholar
  97. Shingo T, Gregg C, Enwere E, Fujikawa H, Hassam R, Geary C, Cross J C, Weiss S (2003). Pregnancy-stimulated neurogenesis in the adult female forebrain mediated by prolactin. Science, 299(5603): 117–120PubMedGoogle Scholar
  98. Song J, Zhong C, Bonaguidi M A, Sun G J, Hsu D, Gu Y, Meletis K, Huang Z J, Ge S, Enikolopov G, Deisseroth K, Luscher B, Christian K M, Ming G L, Song H (2012). Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision. Nature, 489(7414): 150–154PubMedGoogle Scholar
  99. Speisman R B, Kumar A, Rani A, Foster T C, Ormerod B K (2013). Daily exercise improves memory, stimulates hippocampal neurogenesis and modulates immune and neuroimmune cytokines in aging rats. Brain Behav Immun, 28: 25–43PubMedGoogle Scholar
  100. Squire L R (2009). The legacy of patient H.M. for neuroscience. Neuron, 61(1): 6–9PubMedGoogle Scholar
  101. Suijo K, Inoue S, Ohya Y, Odagiri Y, Takamiya T, Ishibashi H, Itoh M, Fujieda Y, Shimomitsu T (2012). Resistance exercise enhances cognitive function in mouse. Int J Sports MedGoogle Scholar
  102. Suwabe T, Mistretta CM, Bradley RM (2013). Excitatory and inhibitory synaptic function in the rostral nucleus of the solitary tract in embryonic rat. Brain Res, 1490: 117–127PubMedGoogle Scholar
  103. Szabadits E, Cserép C, Szonyi A, Fukazawa Y, Shigemoto R, Watanabe M, Itohara S, Freund T F, Nyiri G (2011). NMDA receptors in hippocampal GABAergic synapses and their role in nitric oxide signaling. J Neurosci, 31(16): 5893–5904PubMedGoogle Scholar
  104. Tepavčević V, Lazarini F, Alfaro-Cervello C, Kerninon C, Yoshikawa K, GarcÍa-Verdugo J M, Lledo P M, Nait-Oumesmar B, Baron-Van Evercooren A (2011). Inflammation-induced subventricular zone dysfunction leads to olfactory deficits in a targeted mouse model of multiple sclerosis. J Clin Invest, 121(12): 4722–4734PubMedGoogle Scholar
  105. Ueda S, Yoshimoto K, Kadowaki T, Hirata K, Sakakibara S (2010). Improved learning in microencephalic rats. Congenit Anom (Kyoto), 50(1): 58–63Google Scholar
  106. Valeeva G, Valiullina F, Khazipov R (2013). Excitatory actions of GABA in the intact neonatal rodent hippocampus in vitro. Front Cell Neurosci, 7: 20PubMedGoogle Scholar
  107. van den Berge S A, van Strien M E, Korecka J A, Dijkstra A A, Sluijs J A, Kooijman L, Eggers R, De Filippis L, Vescovi A L, Verhaagen J, van de Berg W D, Hol E M (2011). The proliferative capacity of the subventricular zone is maintained in the parkinsonian brain. Brain, 134(Pt 11): 3249–3263PubMedGoogle Scholar
  108. Wang C, Shimizu-Okabe C, Watanabe K, Okabe A, Matsuzaki H, Ogawa T, Mori N, Fukuda A, Sato K (2002). Developmental changes in KCC1, KCC2, and NKCC1 mRNA expressions in the rat brain. Brain Res Dev Brain Res, 139(1): 59–66PubMedGoogle Scholar
  109. Wang D D, Kriegstein A R (2008). GABA regulates excitatory synapse formation in the neocortex via NMDA receptor activation. J Neurosci, 28(21): 5547–5558PubMedGoogle Scholar
  110. Winner B, Kohl Z, Gage F H (2011). Neurodegenerative disease and adult neurogenesis. Eur J Neurosci, 33(6): 1139–1151PubMedGoogle Scholar
  111. Wojtowicz J M (2012). Adult neurogenesis. From circuits to models. Behav Brain Res, 227(2): 490–496PubMedGoogle Scholar
  112. Zhang Y, Liu J, Yao S, Li F, Xin L, Lai M, Bracchi-Ricard V, Xu H, Yen W, Meng W, Liu S, Yang L, Karmally S, Liu J, Zhu H, Gordon J, Khalili K, Srinivasan S, Bethea J R, Mo X, Hu W (2012). Nuclear factor kappa B signaling initiates early differentiation of neural stem cells. Stem Cells, 30(3): 510–524PubMedGoogle Scholar
  113. Zhu L, Polley N, Mathews G C, Delpire E (2008). NKCC1 and KCC2 prevent hyperexcitability in the mouse hippocampus. Epilepsy Res, 79(2–3): 201–212PubMedGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of NeuroscienceTemple University School of MedicinePhiladelphiaUSA
  2. 2.Universidade do Estado do ParáSantarém, PABrasil

Personalised recommendations