title: Role of tonic GABAergic currents during pre- and early postnatal rodent development.
abstract: In the last three decades it became evident that the GABAergic system plays an essential role for the development of the central nervous system, by influencing the proliferation of neuronal precursors, neuronal migration and differentiation, as well as by controlling early activity patterns and thus formation of neuronal networks. GABA controls neuronal development via depolarizing membrane responses upon activation of ionotropic GABA receptors. However, many of these effects occur before the onset of synaptic GABAergic activity and thus require the presence of extrasynaptic tonic currents in neuronal precursors and immature neurons. This review summarizes our current knowledge about the role of tonic GABAergic currents during early brain development. In this review we compare the temporal sequence of the expression and functional relevance of different GABA receptor subunits, GABA synthesizing enzymes and GABA transporters. We also refer to other possible endogenous agonists of GABAA receptors. In addition, we describe functional consequences mediated by the GABAergic system during early developmental periods and discuss current models about the origin of extrasynaptic GABA and/or other endogenous GABAergic agonists during early developmental states. Finally, we present evidence that tonic GABAergic activity is also critically involved in the generation of physiological as well as pathophysiological activity patterns before and after the establishment of functional GABAergic synaptic connections.
authors.affiliation: Institute of Physiology and Pathophysiology, University Medical Center, Johannes Gutenberg University Mainz, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Kilb
authors.forename: Sergei
authors.initials: S
authors.lastname: Kirischuk
authors.forename: Heiko J
authors.initials: HJ
authors.lastname: Luhmann
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D050485:GABA Plasma Membrane Transport Proteins / Q000378:metabolism; D059330:GABAergic Neurons / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D050485:GABA Plasma Membrane Transport Proteins; D005680:gamma-Aminobutyric Acid
keywords: GABA metabolism; GABA transporter; GABAA receptor; GABAB receptor; migration; neuronal proliferation; review; taurine
references.citation: J Neurosci. 2008 May 21;28(21):5547-58
references.pmid: 18495889
references.citation: J Neurophysiol. 2008 Aug;100(2):698-707
references.pmid: 18562558
references.citation: Eur J Neurosci. 2001 Feb;13(3):487-92
references.pmid: 11168555
references.citation: Eur J Neurosci. 2007 Feb;25(3):717-22
references.pmid: 17298599
references.citation: J Physiol. 2006 Sep 1;575(Pt 2):379-87
references.pmid: 16825304
references.citation: Brain Res Dev Brain Res. 2004 Jun 21;150(2):141-50
references.pmid: 15158077
references.citation: J Neurosci. 2006 Nov 8;26(45):11720-5
references.pmid: 17093093
references.citation: Nat Neurosci. 2003 May;6(5):484-90
references.pmid: 12679782
references.citation: Brain Res Mol Brain Res. 1997 Jun;46(1-2):318-20
references.pmid: 9191108
references.citation: Neuron. 1996 Aug;17(2):275-85
references.pmid: 8780651
references.citation: Cell Tissue Res. 2001 Aug;305(2):239-46
references.pmid: 11545261
references.citation: Eur J Neurosci. 2011 Nov;34(10):1677-86
references.pmid: 22103424
references.citation: J Physiol. 2002 Feb 15;539(Pt 1):191-200
references.pmid: 11850512
references.citation: Neurotoxicology. 2007 Sep;28(5):931-7
references.pmid: 17368774
references.citation: Front Cell Neurosci. 2012 Aug 28;6:35
references.pmid: 22973192
references.citation: Neuron. 1997 Feb;18(2):243-55
references.pmid: 9052795
references.citation: J Neurosci. 1999 Jun 15;19(12):4921-37
references.pmid: 10366626
references.citation: Eur J Neurosci. 2010 Oct;32(8):1300-9
references.pmid: 20846322
references.citation: Nature. 2001 Feb 8;409(6821):714-20
references.pmid: 11217860
references.citation: Physiol Rev. 2007 Oct;87(4):1215-84
references.pmid: 17928584
references.citation: J Neurocytol. 2001 May;30(5):391-401
references.pmid: 11951050
references.citation: J Neurosci. 2006 Apr 19;26(16):4216-27
references.pmid: 16624942
references.citation: Neuropharmacology. 2002 Sep;43(4):726-36
references.pmid: 12367618
references.citation: Neuron. 2002 Dec 19;36(6):1051-61
references.pmid: 12495621
references.citation: Neuroscience. 2002;112(2):299-307
references.pmid: 12044448
references.citation: Front Cell Neurosci. 2012 Dec 03;6:57
references.pmid: 23227002
references.citation: J Neurosci. 2005 May 11;25(19):4755-65
references.pmid: 15888651
references.citation: J Physiol. 2009 May 1;587(Pt 9):1873-9
references.pmid: 19153158
references.citation: Brain Res Dev Brain Res. 1997 Mar 17;99(1):1-19
references.pmid: 9088561
references.citation: J Neurosci. 2005 Jun 1;25(22):5280-9
references.pmid: 15930375
references.citation: Cereb Cortex. 1995 May-Jun;5(3):234-46
references.pmid: 7613079
references.citation: Front Cell Neurosci. 2010 Jul 14;4:
references.pmid: 20725525
references.citation: Cereb Cortex. 2000 Sep;10(9):899-909
references.pmid: 10982750
references.citation: J Physiol. 1989 Sep;416:303-25
references.pmid: 2575165
references.citation: J Comp Neurol. 1992 Dec 22;326(4):501-26
references.pmid: 1484122
references.citation: J Neurochem. 2007 Feb;100(3):822-40
references.pmid: 17144904
references.citation: J Neurosci. 2001 Apr 1;21(7):2343-60
references.pmid: 11264309
references.citation: Eur J Neurosci. 2002 Jun;15(11):1747-58
references.pmid: 12081654
references.citation: Neurochem Int. 1996 Oct;29(4):335-56
references.pmid: 8939442
references.citation: J Physiol. 2007 Jun 1;581(Pt 2):515-28
references.pmid: 17317750
references.citation: Eur J Neurosci. 2006 Jan;23(2):514-20
references.pmid: 16420458
references.citation: Neuroscience. 1999;91(4):1223-45
references.pmid: 10391431
references.citation: Curr Opin Neurobiol. 2007 Jun;17(3):298-303
references.pmid: 17433877
references.citation: Neuron. 2012 Jan 12;73(1):23-34
references.pmid: 22243744
references.citation: Coll Antropol. 2008 Jan;32 Suppl 1:9-17
references.pmid: 18405052
references.citation: J Comp Neurol. 1998 Dec 7;402(1):62-74
references.pmid: 9831046
references.citation: Nat Rev Neurosci. 2002 Sep;3(9):715-27
references.pmid: 12209120
references.citation: Eur J Neurosci. 2004 Nov;20(10):2749-56
references.pmid: 15548218
references.citation: J Neurosci. 1996 Nov 1;16(21):6919-32
references.pmid: 8824330
references.citation: Eur J Neurosci. 1993 Sep 1;5(9):1109-17
references.pmid: 8281317
references.citation: Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13135-40
references.pmid: 20624964
references.citation: Front Cell Neurosci. 2013 Mar 13;7:23
references.pmid: 23494150
references.citation: J Neurosci. 1992 Nov;12(11):4151-72
references.pmid: 1331359
references.citation: Eur J Neurosci. 2007 Aug;26(3):537-46
references.pmid: 17686035
references.citation: Annu Rev Neurosci. 2010;33:23-48
references.pmid: 20201645
references.citation: Brain Res Dev Brain Res. 2004 Jul 19;151(1-2):87-98
references.pmid: 15246695
references.citation: Anat Embryol (Berl). 1986;174(1):115-22
references.pmid: 2422983
references.citation: J Neurosci. 1995 Mar;15(3 Pt 2):2547-60
references.pmid: 7891188
references.citation: J Neurosci. 2004 Jun 30;24(26):5877-80
references.pmid: 15229234
references.citation: Neuroreport. 2011 Jul 13;22(10):509-13
references.pmid: 21666516
references.citation: J Neurosci. 2011 Oct 12;31(41):14677-87
references.pmid: 21994384
references.citation: J Neurosci. 1992 Oct;12(10):3935-45
references.pmid: 1403091
references.citation: J Neurophysiol. 2003 Sep;90(3):1363-74
references.pmid: 12966170
references.citation: Trends Neurosci. 2005 Jun;28(6):278-83
references.pmid: 15927682
references.citation: Science. 1997 Oct 17;278(5337):474-6
references.pmid: 9334308
references.citation: Neuroscientist. 2007 Jun;13(3):268-79
references.pmid: 17519369
references.citation: J Neurosci. 2010 Feb 3;30(5):1582-94
references.pmid: 20130169
references.citation: Front Cell Neurosci. 2013 Mar 05;7:20
references.pmid: 23467988
references.citation: Early Hum Dev. 1991 Jul;26(1):61-7
references.pmid: 1914989
references.citation: Nature. 2006 Jan 5;439(7072):79-83
references.pmid: 16327778
references.citation: J Neurosci. 2008 Feb 20;28(8):1854-64
references.pmid: 18287502
references.citation: J Membr Biol. 1998 Aug 1;164(3):239-51
references.pmid: 9691117
references.citation: J Neurophysiol. 2003 Jun;89(6):3155-67
references.pmid: 12611945
references.citation: J Comp Neurol. 1996 Apr 08;367(3):413-30
references.pmid: 8698901
references.citation: J Neurophysiol. 1999 Aug;82(2):570-83
references.pmid: 10444657
references.citation: Neuron. 2000 Dec;28(3):727-40
references.pmid: 11163262
references.citation: Neuroscience. 1986 Oct;19(2):465-93
references.pmid: 3022187
references.citation: Neuroscientist. 2012 Dec;18(6):613-30
references.pmid: 21952258
references.citation: Neuroscience. 2003;117(2):337-46
references.pmid: 12614674
references.citation: Neuron. 2006 May 18;50(4):575-87
references.pmid: 16701208
references.citation: Nat Commun. 2011 Jul 05;2:376
references.pmid: 21730957
references.citation: J Neurosci. 1992 Aug;12(8):2888-900
references.pmid: 1322978
references.citation: Nat Rev Neurosci. 2002 Sep;3(9):728-39
references.pmid: 12209121
references.citation: J Neurosci. 2002 Apr 15;22(8):3161-73
references.pmid: 11943818
references.citation: Nature. 1990 Aug 16;346(6285):648-51
references.pmid: 2166916
references.citation: Cereb Cortex. 2011 Aug;21(8):1792-802
references.pmid: 21148088
references.citation: Eur J Pharmacol. 2004 Aug 23;497(2):139-46
references.pmid: 15306198
references.citation: Nat Neurosci. 2005 Sep;8(9):1179-87
references.pmid: 16116450
references.citation: J Neurosci. 2009 Oct 28;29(43):13720-9
references.pmid: 19864584
references.citation: J Neurophysiol. 1995 Jan;73(1):246-55
references.pmid: 7714569
references.citation: Neuroscience. 2008 Feb 19;151(4):1119-31
references.pmid: 18248902
references.citation: J Neurophysiol. 1993 Jul;70(1):448-52
references.pmid: 8395587
references.citation: J Physiol. 1998 Feb 15;507 ( Pt 1):219-36
references.pmid: 9490842
references.citation: J Neurochem. 2008 Jun;105(5):1781-93
references.pmid: 18248614
references.citation: J Neurochem. 1967 May;14(5):561-70
references.pmid: 6025625
references.citation: Cereb Cortex. 2001 Aug;11(8):744-53
references.pmid: 11459764
references.citation: J Neurosci. 2007 Aug 8;27(32):8616-27
references.pmid: 17687039
references.citation: J Neurophysiol. 2000 Jan;83(1):359-66
references.pmid: 10634879
references.citation: J Cell Physiol. 2008 Aug;216(2):507-19
references.pmid: 18302163
references.citation: Eur J Neurosci. 2006 May;23(9):2330-8
references.pmid: 16706841
references.citation: Trends Neurosci. 2006 Jul;29(7):414-418
references.pmid: 16713634
references.citation: Cereb Cortex. 2003 Sep;13(9):932-42
references.pmid: 12902392
references.citation: Neuroscience. 2004;123(3):715-24
references.pmid: 14706783
references.citation: Front Cell Neurosci. 2009 Feb 26;3:1
references.pmid: 19277216
references.citation: Neuron. 1991 Dec;7(6):927-36
references.pmid: 1662520
references.citation: Cereb Cortex. 2007 Jan;17(1):138-48
references.pmid: 16452638
references.citation: Trends Pharmacol Sci. 1998 Dec;19(12):500-5
references.pmid: 9871412
references.citation: Neurochem Res. 2005 Dec;30(12):1615-21
references.pmid: 16362781
references.citation: Eur J Neurosci. 2002 Jul;16(2):197-208
references.pmid: 12169102
references.citation: J Neurophysiol. 1999 May;81(5):2095-102
references.pmid: 10322051
references.citation: Prog Brain Res. 2007;160:59-87
references.pmid: 17499109
references.citation: J Neurosci. 1999 Dec 1;19(23):10372-82
references.pmid: 10575034
references.citation: Cereb Cortex. 2006 Oct;16(10):1377-88
references.pmid: 16339085
references.citation: J Neurosci. 1989 Feb;9(2):648-56
references.pmid: 2918382
references.citation: Neuron. 1998 Jan;20(1):43-53
references.pmid: 9459441
references.citation: J Neurosci. 1994 Sep;14(9):5302-24
references.pmid: 8083738
references.citation: J Neurophysiol. 1998 Mar;79(3):1341-8
references.pmid: 9497415
references.citation: J Neurosci. 2000 Aug 1;20(15):5764-74
references.pmid: 10908617
references.citation: Biochem Mol Biol Int. 1997 Jun;42(1):193-202
references.pmid: 9192100
references.citation: Front Cell Neurosci. 2010 Apr 14;4:11
references.pmid: 20428495
references.citation: Brain Res Brain Res Rev. 2004 Jul;45(3):196-212
references.pmid: 15210304
references.citation: J Neurosci. 1996 Oct 15;16(20):6414-23
references.pmid: 8815920
references.citation: Epilepsia. 2012 May;53(5):888-96
references.pmid: 22432890
references.citation: J Neurosci. 1984 Mar;4(3):860-7
references.pmid: 6707735
references.citation: Eur J Neurosci. 2002 Jun;15(11):1766-78
references.pmid: 12081656
references.citation: J Comp Neurol. 1997 Apr 21;380(4):495-506
references.pmid: 9087528
references.citation: J Comp Neurol. 1989 Nov 8;289(2):213-27
references.pmid: 2808764
references.citation: Neurosci Lett. 1993 Apr 2;152(1-2):150-4
references.pmid: 8390627
references.citation: Science. 2000 Feb 4;287(5454):864-9
references.pmid: 10657302
references.citation: J Neurophysiol. 2011 Oct;106(4):2034-44
references.pmid: 21775719
references.citation: Trends Pharmacol Sci. 2000 Jan;21(1):16-9
references.pmid: 10637650
references.citation: J Comp Neurol. 1996 Dec 16;376(3):431-46
references.pmid: 8956109
references.citation: Neurochem Int. 2012 May;60(6):597-604
references.pmid: 22391325
references.citation: Neurosci Res. 1999 Mar;33(3):187-94
references.pmid: 10211762
references.citation: Neuroscience. 2010 Apr 28;167(1):124-34
references.pmid: 20123002
references.citation: Eur J Neurosci. 2011 Aug;34(3):362-73
references.pmid: 21722213
references.citation: Dev Neurosci. 2003 Sep-Oct;25(5):366-74
references.pmid: 14614264
references.citation: J Neurophysiol. 1991 Feb;65(2):247-63
references.pmid: 1673153
references.citation: Neuroscience. 1991;43(2-3):369-80
references.pmid: 1656319
references.citation: Eur J Neurosci. 2002 Jul;16(2):350-4
references.pmid: 12169116
references.citation: Trends Neurosci. 2000 Sep;23(9):429-35
references.pmid: 10941193
references.citation: Neuroscience. 1992 Dec;51(3):583-91
references.pmid: 1336821
references.citation: J Neurosci. 2008 Apr 30;28(18):4777-84
references.pmid: 18448654
references.citation: J Neurosci. 2011 Feb 16;31(7):2413-20
references.pmid: 21325508
references.citation: Nat Rev Neurosci. 2005 Mar;6(3):215-29
references.pmid: 15738957
references.citation: J Neurosci. 1996 Mar 1;16(5):1808-18
references.pmid: 8774448
references.citation: J Neurosci Res. 1986;15(2):223-39
references.pmid: 2421007
references.citation: J Neurosci. 2007 May 9;27(19):5224-35
references.pmid: 17494709
references.citation: J Physiol. 2010 Jul 1;588(Pt 13):2351-60
references.pmid: 20421290
references.citation: J Comp Neurol. 1994 Apr 22;342(4):571-95
references.pmid: 7913715
references.citation: J Neurosci. 2011 Jul 27;31(30):10948-70
references.pmid: 21795545
references.citation: Neurosci Lett. 1988 Jul 8;89(3):335-41
references.pmid: 3419632
references.citation: Neuroscience. 1991;40(2):375-97
references.pmid: 1851254
references.citation: Epilepsia. 2007 Apr;48(4):684-93
references.pmid: 17437411
references.citation: PLoS One. 2011;6(12):e27048
references.pmid: 22180776
references.citation: Neuron. 1995 Dec;15(6):1287-98
references.pmid: 8845153