title: Electron tomography on γ-aminobutyric acid-ergic synapses reveals a discontinuous postsynaptic network of filaments.
abstract: The regulation of synaptic strength at γ-aminobutyric acid (GABA)-ergic synapses is dependent on the dynamic capture, retention, and modulation of GABA A-type receptors by cytoplasmic proteins at GABAergic postsynaptic sites. How these proteins are oriented and organized in the postsynaptic cytoplasm is not yet established. To better understand these structures and gain further insight into the mechanisms by which they regulate receptor populations at postsynaptic sites, we utilized electron tomography to examine GABAergic synapses in dissociated rat hippocampal cultures. GABAergic synapses were identified and selected for tomography by using a set of criteria derived from the structure of immunogold-labeled GABAergic synapses. Tomography revealed a complex postsynaptic network composed of filaments that extend ∼ 100 nm into the cytoplasm from the postsynaptic membrane. The distribution of these postsynaptic filaments was strikingly similar to that of the immunogold label for gephyrin. Filaments were interconnected through uniform patterns of contact, forming complexes composed of 2-12 filaments each. Complexes did not link to form an integrated, continuous scaffold, suggesting that GABAergic postsynaptic specializations are less rigidly organized than glutamatergic postsynaptic densities.
authors: Laboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, 20892.
authors: Alexander E
authors: AE
authors: Linsalata
authors: Xiaobing
authors: X
authors: Chen
authors: Christine A
authors: CA
authors: Winters
authors: Thomas S
authors: TS
authors: Reese
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D055032:Electron Microscope Tomography; D005614:Freeze Fracturing; D059330:GABAergic Neurons / Q000378:metabolism* / Q000648:ultrastructure*; D005968:Glutamate Decarboxylase / Q000378:metabolism / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism; D009415:Nerve Net / Q000378:metabolism / Q000648:ultrastructure*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000648:ultrastructure*; D013570:Synaptic Membranes / Q000378:metabolism* / Q000648:ultrastructure; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C118623:Slc32a1 protein, rat; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C073441:gephyrin; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2
keywords: gephyrin; glycine receptor; inhibitory synapse; postsynaptic density; γ-aminobutyric acid receptor
references: J Neurosci. 2008 Feb 6;28(6):1356-65
references: 18256255
references: Neuroscience. 1986 Dec;19(4):1045-50
references: 2881226
references: Nat Rev Neurosci. 2001 Apr;2(4):240-50
references: 11283747
references: J Biol Chem. 2012 Apr 13;287(16):12645-56
references: 22351777
references: J Cell Biol. 1977 Jul;74(1):181-203
references: 194906
references: J Neurosci. 1998 Dec 1;18(23):9733-50
references: 9822734
references: Science. 2002 Oct 25;298(5594):776-80
references: 12399578
references: Front Cell Neurosci. 2012 May 15;6:23
references: 22615685
references: Am J Anat. 1967 May;120(3):403-25
references: 6037326
references: Brain Res. 1993 Sep 10;621(2):301-10
references: 8242343
references: J Cell Biol. 1985 Aug;101(2):683-8
references: 2991304
references: J Neurosci. 1995 Jun;15(6):4148-56
references: 7790902
references: Neuroscience. 1998 May;84(1):37-48
references: 9522360
references: Trends Neurosci. 2008 May;31(5):257-64
references: 18403029
references: J Comp Neurol. 1998 Jun 1;395(2):231-44
references: 9603375
references: J Cell Sci. 2007 Apr 15;120(Pt 8):1371-82
references: 17374639
references: J Biol Chem. 2001 Jul 6;276(27):25294-301
references: 11325967
references: J Neurosci. 2006 Aug 16;26(33):8502-11
references: 16914675
references: J Cell Biol. 1974 Nov;63(2 Pt 1):456-65
references: 4419608
references: J Neurosci. 1996 Nov 1;16(21):6919-32
references: 8824330
references: J Biol Chem. 2011 Oct 28;286(43):37702-11
references: 21880742
references: Nat Rev Neurosci. 2004 Oct;5(10):771-81
references: 15378037
references: J Neurosci. 2011 Jul 20;31(29):10481-93
references: 21775594
references: Nat Neurosci. 2001 Mar;4(3):253-60
references: 11224541
references: J Comp Neurol. 1995 Jun 19;357(1):1-14
references: 7673460
references: J Biol Chem. 2007 Feb 23;282(8):5625-32
references: 17182610
references: J Cell Biol. 1987 Apr;104(4):947-56
references: 3031086
references: J Neurosci. 2006 Apr 26;26(17):4586-95
references: 16641238
references: J Mol Biol. 2001 Sep 14;312(2):405-18
references: 11554796
references: J Neurosci. 2005 Nov 9;25(45):10469-78
references: 16280585
references: Brain Res. 1984 Feb 20;293(2):353-9
references: 6320972
references: J Biol Chem. 2006 Oct 6;281(40):30046-56
references: 16882665
references: J Neurosci. 2011 Oct 12;31(41):14677-87
references: 21994384
references: Mol Cell Neurosci. 2012 Feb;49(2):184-95
references: 22146684
references: J Comput Neurosci. 2010 Aug;29(1-2):171-182
references: 19655238
references: Annu Rev Neurosci. 2002;25:103-26
references: 12052905
references: J Comp Neurol. 2012 Aug 15;520(12):2697-711
references: 22684938
references: Mol Cell Neurosci. 1998 Dec;12(6):363-75
references: 9888989
references: Mol Cell Neurosci. 2000 Nov;16(5):566-77
references: 11083919
references: J Neurosci. 1993 Feb;13(2):834-55
references: 8426240
references: Neuroscience. 2006 Sep 1;141(3):1217-24
references: 16757121
references: Brain Res. 1975 Mar 7;85(3):355-71
references: 1089460
references: Cold Spring Harb Perspect Biol. 2011 Dec 01;3(12):
references: 22046028
references: J Biol Chem. 1991 Nov 25;266(33):22242-5
references: 1657993
references: J Cell Sci. 1999 Mar;112 ( Pt 6):811-23
references: 10036231
references: Science. 2003 Oct 17;302(5644):442-5
references: 14564008
references: Structure. 2001 Apr 4;9(4):299-310
references: 11525167
references: J Biol Chem. 1982 Aug 25;257(16):9389-93
references: 6286620
references: Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4453-8
references: 18326622
references: Trends Neurosci. 2002 Nov;25(11):564-70
references: 12392931
references: EMBO J. 2004 Jul 7;23(13):2510-9
references: 15201864
references: J Comp Neurol. 2000 May 15;420(4):481-98
references: 10805922
references: J Cell Biol. 1974 Nov;63(2 Pt 1):441-55
references: 4138148
references: J Anat. 1959 Oct;93:420-33
references: 13829103
references: J Neurosci. 2008 Sep 17;28(38):9321-7
references: 18799665
references: Brain Res. 1968 Jul;9(2):268-87
references: 4175993
references: J Neurosci. 2011 Apr 27;31(17):6329-38
references: 21525273
references: Mol Cell Neurosci. 2004 Dec;27(4):394-403
references: 15555918
references: J Comp Neurol. 1975 Dec 1;164(3):305-21
references: 1184786
references: Pharmacol Ther. 2004 Jun;102(3):195-221
references: 15246246
references: J Neurosci. 1994 Mar;14(3 Pt 2):1834-55
references: 8126575
references: Neuron. 1995 Sep;15(3):563-72
references: 7546736
references: J Neurosci. 1996 May 15;16(10):3166-77
references: 8627355
references: Eur J Neurosci. 1995 Jan 1;7(1):1-11
references: 7711926
references: Trends Neurosci. 2000 Sep;23(9):429-35
references: 10941193
references: Mol Cell Neurosci. 2003 Jun;23(2):264-78
references: 12812758
references: Neuron. 1992 Jun;8(6):1161-70
references: 1319186
references: J Neurosci. 2009 Jun 17;29(24):7639-48
references: 19535575
references: J Neurosci. 1993 Jun;13(6):2371-81
references: 8388921
references: Nature. 1997 Oct 23;389(6653):870-6
references: 9349821
references: J Comp Neurol. 1995 Jun 5;356(3):418-32
references: 7642803
references: J Biol Chem. 2010 Sep 17;285(38):29623-31
references: 20622020