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Metabolic Brain Disease

, Volume 30, Issue 2, pp 367–379 | Cite as

GABA receptors in brain development, function, and injury

Review Article

Abstract

This review presents a brief overview of the γ-aminobutyric acid (GABA) system in the developing and mature central nervous system (CNS) and its potential connections to pathologies of the CNS. γ-aminobutyric acid (GABA) is a major neurotransmitter expressed from the embryonic stage and throughout life. At an early developmental stage, GABA acts in an excitatory manner and is implicated in many processes of neurogenesis, including neuronal proliferation, migration, differentiation, and preliminary circuit-building, as well as the development of critical periods. In the mature CNS, GABA acts in an inhibitory manner, a switch mediated by chloride/cation transporter expression and summarized in this review. GABA also plays a role in the development of interstitial neurons of the white matter, as well as in oligodendrocyte development. Although the underlying cellular mechanisms are not yet well understood, we present current findings for the role of GABA in neurological diseases with characteristic white matter abnormalities, including anoxic-ischemic injury, periventricular leukomalacia, and schizophrenia. Development abnormalities of the GABAergic system appear particularly relevant in the etiology of schizophrenia. This review also covers the potential role of GABA in mature brain injury, namely transient ischemia, stroke, and traumatic brain injury/post-traumatic epilepsy.

Keywords

γ-aminobutyric acid receptors Chloride transporters Anoxic-ischemic injury Periventricular leukomalacia Schizophrenia Stroke 

Notes

Acknowledgments

This work was supported in part by NIH grant R01NS38118, R01NS075995 (D. Sun).

References

  1. Akbarian S, Huang H-S (2006) Molecular and cellular mechanisms of altered GAD1/GAD67 expression in schizophrenia and related disorders. Brain Res Rev 52(2):293–304. doi: 10.1016/j.brainresrev.2006.04.001 CrossRefPubMedGoogle Scholar
  2. Allain A-E, Baїri A, Meyrand P, Branchereau P (2004) Ontogenic changes of the GABAergic system in the embryonic mouse spinal cord. Brain Res 1000(1–2):134–147. doi: 10.1016/j.brainres.2003.11.071 CrossRefPubMedGoogle Scholar
  3. Anderson SA (1997) Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes. Science 278(5337):474–476. doi: 10.1126/science.278.5337.474 CrossRefPubMedGoogle Scholar
  4. Anderson SA, Volk DW, Lewis DA (1996) Increased density of microtubule associated protein 2-immunoreactive neurons in the prefrontal white matter of schizophrenic subjects. Schizophr Res 19(2–3):111–119. doi: 10.1016/0920-9964(96)88521-5 CrossRefPubMedGoogle Scholar
  5. Anderson SA, Kaznowski CE, Horn C, Rubenstein JLR, McConnell SK (2002) Distinct origins of neocortical projection neurons and interneurons in vivo. Cereb Cortex 12(7):702–709CrossRefPubMedGoogle Scholar
  6. Antonopoulos J, Pappas IS, Parnavelas JG (1997) Activation of the GABAA receptor inhibits the proliferative effects of bFGF in cortical progenitor cells. Eur J Neurosci 9(2):291–298CrossRefPubMedGoogle Scholar
  7. Barnard EA, Skolnick P, Olsen RW, Mohler H, Sieghart W, Biggio G, Braestrup C, Bateson AN, Langer SZ (1998) International Union of Pharmacology. XV. Subtypes of Γ-aminobutyric acidA receptors: classification on the basis of subunit structure and receptor function. Pharmacol Rev 50(2):291–314PubMedGoogle Scholar
  8. Barres BA, Koroshetz WJ, Swartz KJ, Chun LL, Corey DP (1990) Ion channel expression by white matter glia: the O-2A glial progenitor cell. Neuron 4(4):507–524CrossRefPubMedGoogle Scholar
  9. Behar TN, Schaffner AE, Scott CA, O’Connell C, Barker JL (1998) Differential response of cortical plate and ventricular zone cells to GABA as a migration stimulus. J Neurosci 18(16):6378–6387PubMedGoogle Scholar
  10. Ben-Ari Y, Tseeb V, Raggozzino D, Khazipov R, Gaiarsa JL (1994) Gamma-aminobutyric acid (GABA): a fast excitatory transmitter which may regulate the development of hippocampal neurones in early postnatal life. Prog Brain Res 102:261–273. doi: 10.1016/S0079-6123(08)60545-2 CrossRefPubMedGoogle Scholar
  11. Ben-Ari Y, Khalilov I, Represa A, Gozlan H (2004) Interneurons set the tune of developing networks. Trends Neurosci 27(7):422–427. doi: 10.1016/j.tins.2004.05.002 CrossRefPubMedGoogle Scholar
  12. Benes FM, Vincent SL, Marie A, Khan Y (1996) Up-regulation of GABAA receptor binding on neurons of the prefrontal cortex in schizophrenic subjects. Neuroscience 75(4):1021–1031CrossRefPubMedGoogle Scholar
  13. Billiards SS, Haynes RL, Folkerth RD, Borenstein NS, Trachtenberg FL, Rowitch DH, Ligon KL, Volpe JJ, Kinney HC (2008) Myelin abnormalities without oligodendrocyte loss in periventricular leukomalacia. Brain Pathol 18(2):153–163. doi: 10.1111/j.1750-3639.2007.00107.x
  14. Blednov YA, Benavidez JM, Black M, Leiter CR, Osterndorff-Kahanek E, Johnson D, Borghese CM et al (2014) GABAA receptors containing ρ1 subunits contribute to in vivo effects of ethanol in mice. PLoS ONE 9(1)Google Scholar
  15. Boue-Grabot E, Roudbaraki M, Bascles L, Tramu G, Bloch B, Garret M (1998) Expression of GABA receptor rho subunits in rat brain. J Neurochem 70(3):899–907CrossRefPubMedGoogle Scholar
  16. Cancedda L, Fiumelli H, Chen K, Poo M (2007) Excitatory GABA action is essential for morphological maturation of cortical neurons in vivo. J Neurosci 27(19):5224–5235. doi: 10.1523/JNEUROSCI.5169-06.2007 CrossRefPubMedGoogle Scholar
  17. Chagnac-Amitai Y, Connors BW (1989) Horizontal spread of synchronized activity in neocortex and its control by GABA-mediated inhibition. J Neurophysiol 61(4):747–758PubMedGoogle Scholar
  18. Chen G, Trombley PQ, van den Pol AN (1995) GABA receptors precede glutamate receptors in hypothalamic development; differential regulation by astrocytes. J Neurophysiol 74(4):1473–1484PubMedGoogle Scholar
  19. Chun JM, Shatz CJ (1989) Interstitial cells of the adult neocortical white matter are the remnant of the early generated subplate neuron population. J Comp Neurol 282(4):555–569CrossRefPubMedGoogle Scholar
  20. Clarkson AN, Huang BS, MacIsaac SE, Mody I, Carmichael ST (2010) Reducing excessive GABAergic tonic inhibition promotes post-stroke functional recovery. Nature 468(7321):305–309CrossRefPubMedCentralPubMedGoogle Scholar
  21. Connor CM, Crawford BC, Akbarian S (2011) White matter neuron alterations in schizophrenia and related disorders. Int J Dev Neurosci Off J Int Soc Dev Neurosci 29(3):325–334. doi: 10.1016/j.ijdevneu.2010.07.236 CrossRefGoogle Scholar
  22. Costa E, Davis J, Grayson DR, Guidotti A, Pappas GD, Pesold C (2001) Dendritic spine hypoplasticity and downregulation of reelin and GABAergic tone in schizophrenia vulnerability. Neurobiol Dis 8(5):723–742. doi: 10.1006/nbdi.2001.0436 CrossRefPubMedGoogle Scholar
  23. Couve A, Moss SJ, Pangalos MN (2000) GABAB receptors: a new paradigm in G protein signaling. Mol Cell Neurosci 16(4):296–312. doi: 10.1006/mcne.2000.0908 CrossRefPubMedGoogle Scholar
  24. Del Rio JA, Soriano E, Ferrer I (1992) Development of GABA-immunoreactivity in the neocortex of the mouse. J Comp Neurol 326(4):501–526CrossRefPubMedGoogle Scholar
  25. Druga R (2009) Neocortical inhibitory system. Folia Biol 55(6):201–217Google Scholar
  26. Eastwood SL, Harrison PJ (2003) Interstitial white matter neurons express less reelin and are abnormally distributed in schizophrenia: towards an integration of molecular and morphologic aspects of the neurodevelopmental hypothesis. Mol Psychiatry 8(9):821–831. doi: 10.1038/sj.mp.4001371 CrossRefGoogle Scholar
  27. Fern R, Waxman SG, Ransom BR (1994) Modulation of anoxic injury in CNS white matter by adenosine and interaction between adenosine and GABA. J Neurophysiol 72(6):2609–2616PubMedGoogle Scholar
  28. Fern R, Waxman SG, Ransom BR (1995) Endogenous GABA attenuates CNS white matter dysfunction following anoxia. J Neurosci Off J Soc Neurosci 15(1 Pt 2):699–708Google Scholar
  29. Harauzov A, Spolidoro M, DiCristo G, De Pasquale R, Cancedda L, Pizzorusso T, Viegi A, Berardi N, Maffei L (2010) Reducing intracortical inhibition in the adult visual cortex promotes ocular dominance plasticity. J Neurosci 30(1):361–371CrossRefPubMedGoogle Scholar
  30. Harayama N, Shibuya I, Tanaka K, Kabashima N, Ueta Y, Yamashita H (1998) Inhibition of N- and P/Q-type calcium channels by postsynaptic GABAB receptor activation in rat supraoptic neurones. J Physiol 509(2):371–383. doi: 10.1111/j.1469-7793.1998.371bn.x CrossRefPubMedCentralPubMedGoogle Scholar
  31. Haydar TF, Wang F, Schwartz ML, Rakic P (2000) Differential modulation of proliferation in the neocortical ventricular and subventricular zones. J Neurosci 20(15):5764–5774PubMedCentralPubMedGoogle Scholar
  32. Haynes RL, Gang X, Folkerth RD, Trachtenberg FL, Volpe JJ, Kinney HC (2011) Potential neuronal repair in cerebral white matter injury in the human neonate. Pediatr Res 69(1):62–67. doi: 10.1203/PDR.0b013e3181ff3792 CrossRefPubMedCentralPubMedGoogle Scholar
  33. Hennou S, Khalilov I, Diabira D, Ben-Ari Y, Gozlan H (2002) Early sequential formation of functional GABAA and glutamatergic synapses on CA1 interneurons of the rat foetal hippocampus. Eur J Neurosci 16(2):197–208. doi: 10.1046/j.1460-9568.2002.02073.x CrossRefPubMedGoogle Scholar
  34. Hensch TK, Stryker MP (2004) Columnar architecture sculpted by GABA circuits in developing cat visual cortex. Science 303(5664):1678–1681. doi: 10.1126/science.1091031
  35. Hübner CA, Stein V, Hermans-Borgmeyer I, Meyer T, Ballanyi K, Jentsch TJ (2001) Disruption of KCC2 reveals an essential role of K-Cl cotransport already in early synaptic inhibition. Neuron 30(2):515–524. doi: 10.1016/S0896-6273(01)00297-5 CrossRefPubMedGoogle Scholar
  36. Hunt RF, Boychuk JA, Smith BN (2013) Neural circuit mechanisms of post-traumatic epilepsy. Front Cell Neurosci 7:89. doi: 10.3389/fncel.2013.00089 CrossRefPubMedCentralPubMedGoogle Scholar
  37. Hyde TM, Lipska BK, Ali T, Mathew SV, Law AJ, Metitiri OE, Straub RE et al (2011) Expression of GABA signaling molecules KCC2, NKCC1, and GAD1 in cortical development and schizophrenia. J Neurosci 31(30):11088–11095CrossRefPubMedCentralPubMedGoogle Scholar
  38. Iwai Y, Fagiolini M, Obata K, Hensch TK (2003) Rapid critical period induction by tonic inhibition in visual cortex. J Neurosci 23(17):6695–6702PubMedGoogle Scholar
  39. Joshi D, Fung SJ, Rothwell A, Weickert CS (2012) Higher gamma-aminobutyric acid neuron density in the white matter of orbital frontal cortex in schizophrenia. Biol Psychiatry 72(9):725–733CrossRefPubMedGoogle Scholar
  40. Jovanovic JN, Thomson AM (2011) Development of cortical GABAergic innervation. Front Cell Neurosci 5:14. doi: 10.3389/fncel.2011.00014 CrossRefPubMedCentralPubMedGoogle Scholar
  41. Judaš M, Sedmak G, Pletikos M, Jovanov-Milošević N (2010) Populations of subplate and interstitial neurons in fetal and adult human telencephalon. J Anat 217(4):381–399. doi: 10.1111/j.1469-7580.2010.01284.x CrossRefPubMedCentralPubMedGoogle Scholar
  42. Káradóttir R, Attwell D (2007) Neurotransmitter receptors in the life and death of oligodendrocytes. Neuroscience 145(4):1426–1438. doi: 10.1016/j.neuroscience.2006.08.070 CrossRefPubMedCentralPubMedGoogle Scholar
  43. Kasyanov AM, Safiulina VF, Voronin LL, Cherubini E (2004) GABA-mediated giant depolarizing potentials as coincidence detectors for enhancing synaptic efficacy in the developing hippocampus. Proc Natl Acad Sci U S A 101(11):3967–3972. doi: 10.1073/pnas.0305974101 CrossRefPubMedCentralPubMedGoogle Scholar
  44. Kilb W (2012) Development of the GABAergic system from birth to adolescence. Neuroscientist Rev J Bringing Neurobiol Neurol Psychiatry 18(6):613–630. doi: 10.1177/1073858411422114 Google Scholar
  45. Kinney HC, Haynes RL, Xu G, Andiman SE, Folkerth RD, Sleeper LA, Volpe JJ (2012) Neuron deficit in the white matter and subplate in periventricular leukomalacia. Ann Neurol 71(3):397–406CrossRefPubMedCentralPubMedGoogle Scholar
  46. Koós T, Tepper JM (1999) Inhibitory control of neostriatal projection neurons by GABAergic interneurons. Nat Neurosci 2(5):467–472. doi: 10.1038/8138 CrossRefPubMedGoogle Scholar
  47. Lee V, Maguire J (2014) The impact of tonic GABAA receptor-mediated inhibition on neuronal excitability varies across brain region and cell type. Front Neural Circ 8. doi: 10.3389/fncir.2014.00003
  48. Letinic K, Zoncu R, Rakic P (2002) Origin of GABAergic neurons in the human neocortex. Nature 417(6889):645–649. doi: 10.1038/nature00779 CrossRefPubMedGoogle Scholar
  49. Leto K, Bartolini A, Yanagawa Y, Obata K, Magrassi L, Schilling K, Rossi F (2009) Laminar fate and phenotype specification of cerebellar GABAergic interneurons. J Neurosci 29(21):7079–7091. doi: 10.1523/JNEUROSCI.0957-09.2009 CrossRefPubMedGoogle Scholar
  50. Li Y, Lei Z, Xu ZC (2009) Enhancement of inhibitory synaptic transmission in large aspiny neurons after transient cerebral ischemia. Neuroscience 159(2):670–681. doi: 10.1016/j.neuroscience.2008.12.046
  51. Li Y, Blanco GD, Lei Z, Xu ZC (2010) Increased GAD expression in the striatum after transient cerebral ischemia. Mol Cell Neurosci 45(4):370–377CrossRefPubMedCentralPubMedGoogle Scholar
  52. Lin S, Bergles DE (2004) Synaptic signaling between GABAergic interneurons and oligodendrocyte precursor cells in the hippocampus. Nat Neurosci 7(1):24–32. doi: 10.1038/nn1162 CrossRefPubMedGoogle Scholar
  53. Lipton P (1999) Ischemic cell death in brain neurons. Physiol Rev 79(4):1431–1568PubMedGoogle Scholar
  54. López-Bendito G, Luján R, Shigemoto R, Ganter P, Paulsen O, Molnár Z (2003) Blockade of GABAB receptors alters the tangential migration of cortical neurons. Cereb Cortex 13(9):932–942. doi: 10.1093/cercor/13.9.932 CrossRefPubMedGoogle Scholar
  55. LoTurco JJ, Owens DF, Heath MJS, Davis MBE, Kriegstein AR (1995) GABA and glutamate depolarize cortical progenitor cells and inhibit DNA synthesis. Neuron 15(6):1287–1298CrossRefPubMedGoogle Scholar
  56. Luhmann HJ, Prince DA (1990) Control of NMDA receptor-mediated activity by GABAergic mechanisms in mature and developing rat neocortex. Dev Brain Res 54(2):287–290. doi: 10.1016/0165-3806(90)90152-O CrossRefGoogle Scholar
  57. Luján R, Shigemoto R, López-Bendito G (2005) Glutamate and GABA receptor signalling in the developing brain. Neuroscience 130(3):567–580. doi: 10.1016/j.neuroscience.2004.09.042 CrossRefPubMedGoogle Scholar
  58. Luyt K, Slade TP, Dorward JJ, Durant CF, Yue W, Shigemoto R, Mundell SJ, Váradi A, Molnár E (2007) Developing oligodendrocytes express functional GABAB receptors that stimulate cell proliferation and migration. J Neurochem 100(3):822–840. doi: 10.1111/j.1471-4159.2006.04255.x CrossRefPubMedGoogle Scholar
  59. Macdonald RL, Olsen RW (1994) Gabaa receptor channels. Annu Rev Neurosci 17(1):569–602CrossRefPubMedGoogle Scholar
  60. Maloku E, Covelo IR, Hanbauer I, Guidotti A, Kadriu B, Hu Q, Davis JM, Costa E (2010) Lower number of cerebellar purkinje neurons in psychosis is associated with reduced reelin expression. Proc Natl Acad Sci U S A 107(9):4407–4411CrossRefPubMedCentralPubMedGoogle Scholar
  61. Mangin J-M, Gallo V (2011) The curious case of NG2 cells: transient trend or game changer? ASN Neuro 3(1):37–49. doi: 10.1042/AN20110001 CrossRefGoogle Scholar
  62. Marín O, Rubenstein JLR (2001) A long, remarkable journey: tangential migration in the telencephalon. Nat Rev Neurosci 2(11):780–790. doi: 10.1038/35097509 CrossRefPubMedGoogle Scholar
  63. Markram H, Toledo-Rodriguez M, Wang Y, Gupta A, Silberberg G, Caizhi W (2004) Interneurons of the neocortical inhibitory system. Nat Rev Neurosci 5(10):793–807. doi: 10.1038/nrn1519 CrossRefPubMedGoogle Scholar
  64. Miller LG, Galpern WR, Dunlap K, Dinarello CA, Turner TJ (1991) Interleukin-1 augments gamma-aminobutyric acidA receptor function in brain. Mol Pharmacol 39(2):105–108PubMedGoogle Scholar
  65. Misgeld U, Bijak M, Jarolimek W (1995) A physiological role for GABAB receptors and the effects of baclofen in the mammalian central nervous system. Prog Neurobiol 46(4):423–462CrossRefPubMedGoogle Scholar
  66. Mtchedlishvili Z, Lepsveridze E, Xu H, Kharlamov EA, Lu B, Kelly KM (2010) Increase of GABAA receptor-mediated tonic inhibition in dentate granule cells after traumatic brain injury. Neurobiol Dis 38(3):464–475. doi: 10.1016/j.nbd.2010.03.012
  67. Obrietan K, van den Pol AN (1998) GABAB receptor-mediated inhibition of GABAA receptor calcium elevations in developing hypothalamic neurons. J Neurophysiol 79(3):1360–1370PubMedGoogle Scholar
  68. Owens DF, Kriegstein AR (2002) Is there more to gaba than synaptic inhibition? Nat Rev Neurosci 3(9):715–727. doi: 10.1038/nrn919 CrossRefPubMedGoogle Scholar
  69. Pesold C, Impagnatiello F, Pisu MG, Uzunov DP, Costa E, Guidotti A, Caruncho HJ (1998) Reelin is preferentially expressed in neurons synthesizing γ-aminobutyric acid in cortex and hippocampus of adult rats. Proc Natl Acad Sci U S A 95(6):3221–3226CrossRefPubMedCentralPubMedGoogle Scholar
  70. Petanjek Z, Dujmović A, Kostović I, Esclapez M (2008) Distinct origin of GABA-ergic neurons in forebrain of man, nonhuman primates and lower mammals. Coll Antropol 32(Suppl 1):9–17PubMedGoogle Scholar
  71. Petanjek Z, Berger B, Esclapez M (2009) Origins of cortical GABAergic neurons in the cynomolgus monkey. Cereb Cortex 19(2):249–262. doi: 10.1093/cercor/bhn078
  72. Pfeffer CK, Stein V, Keating DJ, Maier H, Rinke I, Rudhard Y, Hentschke M, Rune GM, Jentsch TJ, Hübner CA (2009) NKCC1-dependent GABAergic excitation drives synaptic network maturation during early hippocampal development. J Neurosci 29(11):3419–3430. doi: 10.1523/JNEUROSCI.1377-08.2009 CrossRefPubMedGoogle Scholar
  73. Riccio O, Murthy S, Szabo G, Vutskits L, Kiss JZ, Vitalis T, Lebrand C, Dayer AG (2012) New pool of cortical interneuron precursors in the early postnatal dorsal white matter. Cereb Cortex 22(1):86–98. doi: 10.1093/cercor/bhr086
  74. Rice DS, Curran T (2001) Role of the reelin signaling pathway in central nervous system development. Annu Rev Neurosci 24(1):1005–1039. doi: 10.1146/annurev.neuro.24.1.1005 CrossRefPubMedGoogle Scholar
  75. Rivera C, Voipio J, Payne JA, Ruusuvuori E, Lahtinen H, Lamsa K, Pirvola U, Saarma M, Kaila K (1999) The K+/Cl|[minus]| co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature 397(6716):251–255. doi: 10.1038/16697 CrossRefPubMedGoogle Scholar
  76. Robinson S, Li Q, DeChant A, Cohen ML (2006) Neonatal loss of Γ–aminobutyric acid pathway expression after human perinatal brain injury. J Neurosurg 104(6 Suppl):396PubMedCentralPubMedGoogle Scholar
  77. Rudy B, Fishell G, Lee SH, Hjerling-Leffler J (2011) Three groups of interneurons account for nearly 100 % of neocortical GABAergic neurons. Dev Neurobiol 71(1):45–61. doi: 10.1002/dneu.20853
  78. Segovia KN, McClure M, Moravec M, Luo NL, Wan Y, Gong X, Riddle A et al (2008) Arrested oligodendrocyte lineage maturation in chronic perinatal white matter injury. Ann Neurol 63(4):520–530CrossRefPubMedCentralPubMedGoogle Scholar
  79. Strata F, Atzori M, Molnar M, Ugolini G, Tempia F, Cherubini E (1997) A pacemaker current in dye-coupled hilar interneurons contributes to the generation of giant GABAergic potentials in developing hippocampus. J Neurosci 17(4):1435–1446PubMedGoogle Scholar
  80. Suárez-Solá ML, González-Delgado FJ, Pueyo-Morlans M, Medina-Bolívar OC, Hernández-Acosta NC, González-Gómez M, Meyer G (2009) Neurons in the white matter of the adult human neocortex. Front Neuroanat 3:7. doi: 10.3389/neuro.05.007.2009
  81. Sun D, Murali SG (1999) Na+−K+−2Cl−cotransporter in immature cortical neurons: a role in intracellular Cl−regulation. J Neurophysiol 81(4):1939–1948PubMedGoogle Scholar
  82. Takesian AE, Hensch TK (2013) Chapter 1 - Balancing plasticity/stability across brain development. In: Nahum M, Van Vleet T, Merzenich MM (eds) Progress in brain research, vol 207. Changing brains applying brain plasticity to advance and recover human ability. Elsevier, 3–34. http://www.sciencedirect.com/science/article/pii/B9780444633279000011
  83. Tan S-S, Kalloniatis M, Sturm K, Tam PL, Reese BE, Faulkner-Jones B (1998) Separate progenitors for radial and tangential cell dispersion during development of the cerebral neocortex. Neuron 21(2):295–304CrossRefPubMedGoogle Scholar
  84. Tao R, Li C, Newburn EN, Ye T, Lipska BK, Herman MM, Weinberger DR, Kleinman JE, Hyde TM (2012) Transcript-specific associations of SLC12A5 (KCC2) in human prefrontal cortex with development, schizophrenia, and affective disorders. J Neurosci 32(15):5216–5222. doi: 10.1523/JNEUROSCI.4626-11.2012 CrossRefPubMedCentralPubMedGoogle Scholar
  85. van den Pol AN, Gao XB, Patrylo PR, Ghosh PK, Obrietan K (1998) Glutamate inhibits GABA excitatory activity in developing neurons. J Neurosci 18(24):10749–10761Google Scholar
  86. Wang DD, Kriegstein AR (2009) Defining the role of GABA in cortical development. J Physiol 587(9):1873–1879. doi: 10.1113/jphysiol.2008.167635 CrossRefPubMedCentralPubMedGoogle Scholar
  87. Wang H, Yan Y, Kintner DB, Lytle C, Sun D (2003) GABA-mediated trophic effect on oligodendrocytes requires Na-K-2Cl cotransport activity. J Neurophysiol 90(2):1257–1265. doi: 10.1152/jn.01174.2002 CrossRefPubMedGoogle Scholar
  88. Williams JR, Sharp JW, Kumari VG, Wilson M, Payne JA (1999) The neuron-specific K-Cl cotransporter, KCC2 antibody development and initial characterization of the protein. J Biol Chem 274(18):12656–12664. doi: 10.1074/jbc.274.18.12656 CrossRefPubMedGoogle Scholar
  89. Xu G, Broadbelt KG, Haynes RL, Folkerth RD, Borenstein NS, Belliveau RA, Trachtenberg FL, Volpe JJ, Kinney HC (2011) Late development of the GABAergic system in the human cerebral cortex and white matter. J Neuropathol Exp Neurol 70(10):841–858. doi: 10.1097/NEN.0b013e31822f471c CrossRefPubMedCentralPubMedGoogle Scholar
  90. Yamada J, Okabe A, Toyoda H, Kilb W, Luhmann HJ, Fukuda A (2004) Cl− uptake promoting depolarizing GABA actions in immature rat neocortical neurones is mediated by NKCC1. J Physiol 557(3):829–841. doi: 10.1113/jphysiol.2004.062471 CrossRefPubMedCentralPubMedGoogle Scholar
  91. Yan XX, Jen LS, Garey LJ (1996) NADPH-diaphorase-positive neurons in primate cerebral cortex colocalize with GABA and calcium-binding proteins. Cereb Cortex 6(3):524–529. doi: 10.1093/cercor/6.3.524 CrossRefPubMedGoogle Scholar
  92. Yang Y, Fung SJ, Rothwell A, Tianmei S, Weickert CS (2011) Increased interstitial white matter neuron density in the DLPFC of people with schizophrenia. Biol Psychiatry 69(1):63–70CrossRefPubMedCentralPubMedGoogle Scholar
  93. Yu Z, Fang Q, Xiao X, Wang Y-Z, Cai Y-Q, Cao H, Hu G et al (2013) GABA transporter-1 deficiency confers schizophrenia-like behavioral phenotypes. PLoS ONE 8(7):e69883. doi: 10.1371/journal.pone.0069883 CrossRefPubMedCentralPubMedGoogle Scholar

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of NeuroscienceUniversity of Wisconsin-MadisonMadisonUSA
  2. 2.Department of NeurologyUniversity of Pittsburgh Medical SchoolPittsburghUSA
  3. 3.Veterans Affairs Pittsburgh Health Care SystemGeriatric Research, Educational and Clinical CenterPittsburghUSA

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