title: Elimination of redundant synaptic inputs in the absence of synaptic strengthening.
abstract: Synaptic refinement, a developmental process that consists of selective elimination and strengthening of immature synapses, is essential for the formation of precise neuronal circuits and proper brain function. At glutamatergic synapses in the brain, activity-dependent recruitment of AMPA receptors (AMPARs) is a key mechanism underlying the strengthening of immature synapses. Studies using receptor overexpression have shown that the recruitment of AMPARs is subunit specific. With the notable exception of hippocampal CA3-CA1 synapses, however, little is known about how native receptors behave or the roles of specific AMPAR subunits in synaptic refinement in vivo. Using patch-clamp recordings in acute slices, we examined developmental refinement of whisker relay (lemniscal) synapses in the thalamus in mice deficient of AMPAR subunits. Deletion of GluA3 or GluA4 caused significant reductions of synaptic AMPAR currents in thalamic neurons at P16-P17, with a greater reduction observed in GluA3-deficient mice. Deletions of both GluA3 and GluA4 abolished synaptic AMPAR responses in the majority of thalamic neurons, indicating that at thalamic relay synapses AMPARs are composed primarily of GluA3 and GluA4. Surprisingly, deletions of GluA3 or GluA4 or both had no effect on the elimination of relay inputs: the majority of thalamic neurons in these knock-out mice-as in wild-type mice-receive a single relay input. However, experience-dependent strengthening of thalamic relay synapses was impaired in GluA3 knock-out mice. Together these findings suggest that the elimination of immature glutamatergic synapses proceeds normally in the absence of synaptic strengthening, and highlight the role of GluA3-containing AMPARs in experience-dependent synaptic plasticity.
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Zhong-wei
authors.initials: ZW
authors.lastname: Zhang
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D018091:Receptors, AMPA / Q000172:deficiency; D012683:Sensory Deprivation / Q000502:physiology; D018709:Statistics, Nonparametric; D013569:Synapses / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013788:Thalamus / Q000166:cytology; D015854:Up-Regulation / Q000235:genetics; D014738:Vibrissae / Q000294:innervation
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3; C104724:glutamate receptor ionotropic, AMPA 4; D015763:2-Amino-5-phosphonovalerate
references.citation: Nat Rev Neurosci. 2008 Nov;9(11):813-25
references.pmid: 18854855
references.citation: J Neurophysiol. 2004 Mar;91(3):1171-82
references.pmid: 14602839
references.citation: Curr Opin Neurobiol. 2006 Jun;16(3):288-97
references.pmid: 16713244
references.citation: Trends Neurosci. 2002 Nov;25(11):578-88
references.pmid: 12392933
references.citation: Science. 1996 Nov 8;274(5289):972-6
references.pmid: 8875937
references.citation: J Neurosci. 2005 Oct 5;25(40):9135-43
references.pmid: 16207872
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10702-7
references.pmid: 20498043
references.citation: Nat Neurosci. 2000 Nov;3(11):1098-106
references.pmid: 11036266
references.citation: J Neurosci. 2008 Dec 10;28(50):13621-8
references.pmid: 19074025
references.citation: Neuron. 1997 Feb;18(2):269-80
references.pmid: 9052797
references.citation: Science. 1997 Jan 17;275(5298):356-61
references.pmid: 8994026
references.citation: Neuroscience. 1995 Aug;67(4):881-92
references.pmid: 7545799
references.citation: Neuron. 2003 Oct 9;40(2):361-79
references.pmid: 14556714
references.citation: Neuron. 2007 Jun 21;54(6):859-71
references.pmid: 17582328
references.citation: Annu Rev Neurosci. 2005;28:127-56
references.pmid: 16022592
references.citation: Neuron. 2009 Apr 30;62(2):254-68
references.pmid: 19409270
references.citation: J Comp Neurol. 1997 Sep 15;386(1):29-45
references.pmid: 9303523
references.citation: Annu Rev Neurosci. 1999;22:389-442
references.pmid: 10202544
references.citation: J Neurosci. 2008 Dec 17;28(51):13918-28
references.pmid: 19091980
references.citation: Neuron. 2003 Jun 5;38(5):785-96
references.pmid: 12797962
references.citation: J Neurosci. 2002 Apr 15;22(8):3005-15
references.pmid: 11943803
references.citation: Neuron. 1995 Aug;15(2):427-34
references.pmid: 7646894
references.citation: J Neurosci. 1996 Mar 15;16(6):1982-9
references.pmid: 8604042
references.citation: Neuron. 2002 Nov 14;36(4):635-48
references.pmid: 12441053
references.citation: Nature. 2003 Jul 24;424(6947):430-4
references.pmid: 12879071
references.citation: Neuron. 2000 Dec;28(3):955-66
references.pmid: 11163279
references.citation: Nat Neurosci. 1999 Jan;2(1):31-6
references.pmid: 10195177
references.citation: Annu Rev Neurosci. 2002;25:103-26
references.pmid: 12052905
references.citation: Crit Rev Neurobiol. 2006;18(1-2):49-59
references.pmid: 17725508
references.citation: Nat Rev Neurosci. 2004 Dec;5(12):952-62
references.pmid: 15550950
references.citation: Annu Rev Physiol. 2004;66:161-81
references.pmid: 14977400
references.citation: Curr Opin Neurobiol. 2009 Apr;19(2):154-61
references.pmid: 19481442
references.citation: Neuron. 2000 Feb;25(2):269-78
references.pmid: 10719884
references.citation: J Comp Neurol. 1997 Dec 1;388(4):587-602
references.pmid: 9388018
references.citation: Neuroscience. 2000;101(4):969-82
references.pmid: 11113346
references.citation: J Physiol. 2006 May 15;573(Pt 1):121-32
references.pmid: 16581865
references.citation: Hum Mol Genet. 2008 Jun 15;17(12):1738-49
references.pmid: 18316356
references.citation: Dev Neurosci. 2000;22(4):329-40
references.pmid: 10965155