Skip to main content
SpringerLink
Log in

GABA receptors in brain development, function, and injury

  • Review Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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):702–709

    Article  PubMed  Google Scholar 

  • 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):291–298

    Article  CAS  PubMed  Google Scholar 

  • 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):291–314

    CAS  PubMed  Google Scholar 

  • 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):507–524

    Article  CAS  PubMed  Google Scholar 

  • 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):6378–6387

    CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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):1021–1031

    Article  CAS  PubMed  Google Scholar 

  • 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

  • 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)

  • 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):899–907

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Chagnac-Amitai Y, Connors BW (1989) Horizontal spread of synchronized activity in neocortex and its control by GABA-mediated inhibition. J Neurophysiol 61(4):747–758

    CAS  PubMed  Google Scholar 

  • 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):1473–1484

    CAS  PubMed  Google Scholar 

  • 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):555–569

    Article  CAS  PubMed  Google Scholar 

  • Clarkson AN, Huang BS, MacIsaac SE, Mody I, Carmichael ST (2010) Reducing excessive GABAergic tonic inhibition promotes post-stroke functional recovery. Nature 468(7321):305–309

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Del Rio JA, Soriano E, Ferrer I (1992) Development of GABA-immunoreactivity in the neocortex of the mouse. J Comp Neurol 326(4):501–526

    Article  PubMed  Google Scholar 

  • Druga R (2009) Neocortical inhibitory system. Folia Biol 55(6):201–217

    CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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):2609–2616

    CAS  PubMed  Google Scholar 

  • 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):699–708

    CAS  Google Scholar 

  • 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):361–371

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Haydar TF, Wang F, Schwartz ML, Rakic P (2000) Differential modulation of proliferation in the neocortical ventricular and subventricular zones. J Neurosci 20(15):5764–5774

    PubMed Central  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed Central  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed Central  PubMed  Google Scholar 

  • 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):11088–11095

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Iwai Y, Fagiolini M, Obata K, Hensch TK (2003) Rapid critical period induction by tonic inhibition in visual cortex. J Neurosci 23(17):6695–6702

    CAS  PubMed  Google Scholar 

  • 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):725–733

    Article  CAS  PubMed  Google Scholar 

  • Jovanovic JN, Thomson AM (2011) Development of cortical GABAergic innervation. Front Cell Neurosci 5:14. doi:10.3389/fncel.2011.00014

    Article  PubMed Central  PubMed  Google Scholar 

  • 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

    Article  PubMed Central  PubMed  Google Scholar 

  • 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

    Article  PubMed Central  PubMed  Google Scholar 

  • 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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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):397–406

    Article  PubMed Central  PubMed  Google Scholar 

  • Koós T, Tepper JM (1999) Inhibitory control of neostriatal projection neurons by GABAergic interneurons. Nat Neurosci 2(5):467–472. doi:10.1038/8138

    Article  PubMed  Google Scholar 

  • 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

  • Letinic K, Zoncu R, Rakic P (2002) Origin of GABAergic neurons in the human neocortex. Nature 417(6889):645–649. doi:10.1038/nature00779

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

  • Li Y, Blanco GD, Lei Z, Xu ZC (2010) Increased GAD expression in the striatum after transient cerebral ischemia. Mol Cell Neurosci 45(4):370–377

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Lipton P (1999) Ischemic cell death in brain neurons. Physiol Rev 79(4):1431–1568

    CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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):1287–1298

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Macdonald RL, Olsen RW (1994) Gabaa receptor channels. Annu Rev Neurosci 17(1):569–602

    Article  CAS  PubMed  Google Scholar 

  • 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):4407–4411

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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):105–108

    CAS  PubMed  Google Scholar 

  • 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):423–462

    Article  CAS  PubMed  Google Scholar 

  • 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

  • Obrietan K, van den Pol AN (1998) GABAB receptor-mediated inhibition of GABAA receptor calcium elevations in developing hypothalamic neurons. J Neurophysiol 79(3):1360–1370

    CAS  PubMed  Google Scholar 

  • Owens DF, Kriegstein AR (2002) Is there more to gaba than synaptic inhibition? Nat Rev Neurosci 3(9):715–727. doi:10.1038/nrn919

    Article  CAS  PubMed  Google Scholar 

  • 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):3221–3226

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):9–17

    PubMed  Google Scholar 

  • 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

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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):396

    PubMed Central  PubMed  Google Scholar 

  • 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

  • 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):520–530

    Article  PubMed Central  PubMed  Google Scholar 

  • 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):1435–1446

    CAS  PubMed  Google Scholar 

  • 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

  • Sun D, Murali SG (1999) Na+−K+−2Cl−cotransporter in immature cortical neurons: a role in intracellular Cl−regulation. J Neurophysiol 81(4):1939–1948

    CAS  PubMed  Google Scholar 

  • 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

  • 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):295–304

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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):10749–10761

  • 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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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):63–70

    Article  PubMed Central  PubMed  Google Scholar 

  • 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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

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

Author information

Authors and Affiliations

  1. Department of Neuroscience, University of Wisconsin-Madison, Madison, WI, 53706, USA

    Connie Wu

  2. Department of Neurology, University of Pittsburgh Medical School, S-598 South Biomedical Science Tower (BST), 3500 Terrace St., Pittsburgh, PA, 15213, USA

    Dandan Sun

  3. Veterans Affairs Pittsburgh Health Care System, Geriatric Research, Educational and Clinical Center, Pittsburgh, PA, 15213, USA

    Dandan Sun

Authors
  1. Connie Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dandan Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dandan Sun.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, C., Sun, D. GABA receptors in brain development, function, and injury. Metab Brain Dis 30, 367–379 (2015). https://doi.org/10.1007/s11011-014-9560-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-014-9560-1

Keywords

Search

Navigation