title: GABAergic and glycinergic inhibitory synaptic transmission in the ventral cochlear nucleus studied in VGAT channelrhodopsin-2 mice.
abstract: Both glycine and GABA mediate inhibitory synaptic transmission in the ventral cochlear nucleus (VCN). In mice, the time course of glycinergic inhibition is slow in bushy cells and fast in multipolar (stellate) cells, and is proposed to contribute to the processing of temporal cues in both cell types. Much less is known about GABAergic synaptic transmission in this circuit. Electrical stimulation of the auditory nerve or the tuberculoventral pathway evokes little GABAergic synaptic current in brain slice preparations, and spontaneous GABAergic miniature synaptic currents occur infrequently. To investigate synaptic currents carried by GABA receptors in bushy and multipolar cells, we used transgenic mice in which channelrhodopsin-2 and EYFP is driven by the vesicular GABA transporter (VGAT-ChR2-EYFP) and is expressed in both GABAergic and glycinergic neurons. Light stimulation evoked action potentials in EYFP-expressing presynaptic cells, and evoked inhibitory postsynaptic potentials (IPSPs) in non-expressing bushy and planar multipolar cells. Less than 10% of the IPSP amplitude in bushy cells arose from GABAergic synapses, whereas 40% of the IPSP in multipolar neurons was GABAergic. In voltage clamp, glycinergic IPSCs were significantly slower in bushy neurons than in multipolar neurons, whereas there was little difference in the kinetics of the GABAergic IPSCs between two cell types. During prolonged stimulation, the ratio of steady state vs. peak IPSC amplitude was significantly lower for glycinergic IPSCs. Surprisingly, the reversal potentials of GABAergic IPSCs were negative to those of glycinergic IPSCs in both bushy and multipolar neurons. In the absence of receptor blockers, repetitive light stimulation was only able to effectively evoke IPSCs up to 20 Hz in both bushy and multipolar neurons. We conclude that local GABAergic release within the VCN can differentially influence bushy and multipolar cells.
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill Chapel Hill, NC, USA.
authors.forename: Ruili
authors.initials: R
authors.lastname: Xie
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill Chapel Hill, NC, USA ; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill Chapel Hill, NC, USA.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Manis
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000075402:Channelrhodopsins; D017626:Cochlear Nucleus / Q000166:cytology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism*; D018684:Glycine Agents / Q000494:pharmacology; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D011724:Pyridazines / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013331:Strychnine / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000075402:Channelrhodopsins; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018684:Glycine Agents; D011724:Pyridazines; D026941:Sodium Channel Blockers; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C049853:gabazine; D013331:Strychnine; D005998:Glycine
keywords: IPSC; bushy; multipolar; stellate; target-specific inhibition
references.citation: Neuroscience. 2009 Dec 15;164(3):1031-43
references.pmid: 19766173
references.citation: Hear Res. 1999 Aug;134(1-2):77-88
references.pmid: 10452378
references.citation: J Comp Neurol. 1987 Aug 15;262(3):375-401
references.pmid: 2443543
references.citation: Front Neuroinform. 2014 Jan 30;8:3
references.pmid: 24523692
references.citation: J Cell Sci. 1999 Mar;112 ( Pt 6):811-23
references.pmid: 10036231
references.citation: Neuron. 2006 Jan 5;49(1):81-94
references.pmid: 16387641
references.citation: J Comp Neurol. 1987 Apr 8;258(2):267-80
references.pmid: 3584540
references.citation: J Neurosci. 1991 Sep;11(9):2865-80
references.pmid: 1880553
references.citation: Brain Res Bull. 1986 Feb;16(2):189-203
references.pmid: 3008955
references.citation: Hear Res. 1991 Jan;51(1):11-28
references.pmid: 1672865
references.citation: Brain Res. 1994 Mar 14;639(2):193-201
references.pmid: 8205472
references.citation: J Comp Neurol. 1996 Sep 09;373(1):11-26
references.pmid: 8876459
references.citation: J Assoc Res Otolaryngol. 2004 Jun;5(2):153-70
references.pmid: 15357418
references.citation: Science. 2006 Jan 13;311(5758):233-5
references.pmid: 16410524
references.citation: J Physiol. 1987 Apr;385:243-86
references.pmid: 2443667
references.citation: Brain Res. 1989 Dec 11;504(1):173-9
references.pmid: 2557124
references.citation: J Neurophysiol. 1992 Mar;67(3):738-46
references.pmid: 1315848
references.citation: Hear Res. 2000 Nov;149(1-2):91-105
references.pmid: 11033249
references.citation: J Neurosci. 2014 Feb 5;34(6):2214-30
references.pmid: 24501361
references.citation: Proc R Soc Lond B Biol Sci. 1977 Sep 19;198(1133):345-61
references.pmid: 21395
references.citation: J Neurophysiol. 1998 Apr;79(4):1891-901
references.pmid: 9535956
references.citation: J Comp Neurol. 2009 Oct 1;516(4):241-63
references.pmid: 19634178
references.citation: Science. 2014 Feb 7;343(6171):670-5
references.pmid: 24503855
references.citation: J Comp Neurol. 1997 May 19;381(4):500-12
references.pmid: 9136806
references.citation: Prog Brain Res. 2012;196:29-47
references.pmid: 22341319
references.citation: J Comp Neurol. 1988 Oct 15;276(3):423-35
references.pmid: 2848063
references.citation: Brain Res. 1986 Mar 26;369(1-2):316-20
references.pmid: 3008938
references.citation: Nat Methods. 2011 Sep;8(9):745-52
references.pmid: 21985008
references.citation: J Comp Neurol. 1987 Jun 8;260(2):157-74
references.pmid: 3611403
references.citation: Hear Res. 1995 Nov;91(1-2):160-6
references.pmid: 8647717
references.citation: J Neurophysiol. 2008 Mar;99(3):1077-95
references.pmid: 18199821
references.citation: J Neurosci. 2013 Jan 23;33(4):1598-614
references.pmid: 23345233
references.citation: J Neurosci. 1992 Aug;12(8):3042-53
references.pmid: 1379634
references.citation: J Neurophysiol. 2007 Sep;98(3):1634-44
references.pmid: 17596413
references.citation: J Neurosci. 2009 Sep 16;29(37):11495-510
references.pmid: 19759298
references.citation: Nat Neurosci. 2011 Jan;14(1):100-7
references.pmid: 21076426
references.citation: Anat Embryol (Berl). 1992 Oct;186(5):443-65
references.pmid: 1443654
references.citation: J Neurophysiol. 1994 Nov;72(5):2124-33
references.pmid: 7884448
references.citation: J Neurosci. 1986 Sep;6(9):2691-706
references.pmid: 3746428
references.citation: J Comp Neurol. 1991 Nov 15;313(3):457-68
references.pmid: 1770169
references.citation: J Neurophysiol. 1993 Aug;70(2):781-802
references.pmid: 8410172
references.citation: Brain Res. 1979 Aug 17;172(1):179-85
references.pmid: 466463
references.citation: Exp Brain Res. 1995;104(2):310-22
references.pmid: 7672023
references.citation: J Neurophysiol. 2005 Sep;94(3):1814-24
references.pmid: 15901757
references.citation: Hear Res. 1989 Oct;42(1):97-112
references.pmid: 2584161
references.citation: J Physiol. 2000 Jun 1;525 Pt 2:447-59
references.pmid: 10835046
references.citation: J Neurosci. 1990 Jun;10(6):1762-8
references.pmid: 1972392
references.citation: Biophys J. 2009 Mar 4;96(5):1803-14
references.pmid: 19254539
references.citation: J Comp Neurol. 1989 Apr 22;282(4):595-616
references.pmid: 2723154
references.citation: J Neurophysiol. 1998 Jan;79(1):51-63
references.pmid: 9425176
references.citation: J Neurophysiol. 1996 Jun;75(6):2300-11
references.pmid: 8793743