title: Neuronal pentraxins mediate silent synapse conversion in the developing visual system.
abstract: Neuronal pentraxins (NPs) are hypothesized to play important roles in the recruitment of AMPA receptors (AMPARs) to immature synapses, yet a physiological role for NPs at nascent synapses in vivo has remained elusive. Here we report that the loss of NP1 and NP2 (NP1/2) leads to a dramatic and specific reduction in AMPAR-mediated transmission at developing visual system synapses. In thalamic slices taken from early postnatal mice (<P10) NP1/2 knock-out (KO) neurons displayed severely reduced AMPAR-mediated retinogeniculate transmission. The reduced currents reflected an increased number of silent synapses with no change in quantal amplitude or presynaptic release. These are the first data to demonstrate that NP1/2 are required in vivo for the normal development of AMPAR-mediated transmission. In addition, they suggest a novel role for NP1/2 in silent synapse conversion during a discrete developmental period when visual circuit connections are undergoing eye-specific refinement. After this period, retinogeniculate transmission not only recovered in the knock-outs but became excessive. The enhanced currents were attributable, at least in part, to a deficit in the characteristic elimination of functional inputs that occurs in the developing dLGN. These data indicate that the loss of NP1/2 disrupts several aspects of retinogeniculate development including the initial establishment of AMPAR transmission and the subsequent elimination of inappropriate circuit connections.
authors.affiliation: Department of Ophthalmology, University of California, San Francisco, San Francisco, California 94143, USA.
authors.forename: Selina M
authors.initials: SM
authors.lastname: Koch
authors.forename: Erik M
authors.initials: EM
authors.lastname: Ullian
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005829:Geniculate Bodies / Q000254:growth & development / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000502:physiology; D018091:Receptors, AMPA / Q000378:metabolism; D012160:Retina / Q000254:growth & development / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013788:Thalamus / Q000254:growth & development* / Q000502:physiology; D014795:Visual Pathways / Q000254:growth & development* / Q000502:physiology; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D000099153:Pentraxins
references.citation: J Neurosci. 2002 Jul 1;22(13):5259-64
references.pmid: 12097474
references.citation: Neuron. 2008 Mar 27;57(6):858-71
references.pmid: 18367087
references.citation: J Neurosci. 2002 Sep 1;22(17):7606-16
references.pmid: 12196584
references.citation: J Neurosci. 2006 Jun 7;26(23):6269-81
references.pmid: 16763034
references.citation: Science. 1998 Mar 27;279(5359):2108-12
references.pmid: 9516112
references.citation: J Neurosci. 1999 Aug 15;19(16):7007-24
references.pmid: 10436056
references.citation: Nature. 1966 Dec 10;212(5067):1233-4
references.pmid: 21090447
references.citation: J Neurosci. 2008 Jan 2;28(1):292-303
references.pmid: 18171946
references.citation: J Physiol. 2008 Sep 15;586(18):4363-9
references.pmid: 18617562
references.citation: Science. 1988 Oct 7;242(4875):87-9
references.pmid: 3175636
references.citation: Neuron. 1999 Nov;24(3):673-85
references.pmid: 10595518
references.citation: Nat Neurosci. 2000 Nov;3(11):1098-106
references.pmid: 11036266
references.citation: Vis Neurosci. 2005 Sep-Oct;22(5):661-76
references.pmid: 16332277
references.citation: Neuron. 2007 Jul 5;55(1):87-102
references.pmid: 17610819
references.citation: Trends Neurosci. 2008 Feb;31(2):82-9
references.pmid: 18201773
references.citation: Mol Cell Neurosci. 2005 Jul;29(3):436-52
references.pmid: 15894489
references.citation: Neuron. 2003 Jul 31;39(3):513-28
references.pmid: 12895424
references.citation: J Neurosci. 2003 Apr 15;23(8):3130-5
references.pmid: 12716920
references.citation: J Neurophysiol. 2006 Nov;96(5):2775-84
references.pmid: 16899631
references.citation: Nature. 1988 Dec 1;336(6198):468-71
references.pmid: 2461517
references.citation: J Biol Chem. 2000 Jun 9;275(23):17786-92
references.pmid: 10748068
references.citation: J Neurophysiol. 2003 Aug;90(2):1063-70
references.pmid: 12711717
references.citation: J Neurochem. 2002 Aug;82(4):935-44
references.pmid: 12358799
references.citation: Neuron. 2002 Jul 18;35(2):345-53
references.pmid: 12160751
references.citation: Neuron. 1999 Jun;23(2):309-23
references.pmid: 10399937
references.citation: Nat Neurosci. 2003 Jan;6(1):15-6
references.pmid: 12469130
references.citation: J Neurophysiol. 2008 Feb;99(2):629-43
references.pmid: 18032559
references.citation: J Neurophysiol. 2008 Dec;100(6):3253-63
references.pmid: 18922954
references.citation: Philos Trans R Soc Lond B Biol Sci. 2002 Dec 29;357(1428):1759-66
references.pmid: 12626010
references.citation: Science. 2000 Dec 15;290(5499):2155-9
references.pmid: 11118151
references.citation: Mol Cell Neurosci. 2003 Dec;24(4):972-83
references.pmid: 14697662
references.citation: Science. 2003 May 9;300(5621):994-8
references.pmid: 12738869
references.citation: Neuron. 2000 Dec;28(3):955-66
references.pmid: 11163279
references.citation: Neuron. 2006 Oct 19;52(2):281-91
references.pmid: 17046691
references.citation: Cell. 2007 Dec 14;131(6):1164-78
references.pmid: 18083105
references.citation: Neuron. 2005 Jun 2;46(5):745-60
references.pmid: 15924861
references.citation: J Comp Neurol. 1984 Dec 20;230(4):552-75
references.pmid: 6520251
references.citation: J Neurosci Methods. 2004 May 30;135(1-2):17-26
references.pmid: 15020085
references.citation: J Neurosci. 1996 Dec 15;16(24):8181-92
references.pmid: 8987843
references.citation: J Comp Neurol. 1975 Jan 1;159(1):45-67
references.pmid: 45862
references.citation: Nat Neurosci. 2005 Jan;8(1):72-8
references.pmid: 15608630
references.citation: Neuron. 2009 Oct 29;64(2):200-12
references.pmid: 19874788
references.citation: J Physiol. 2004 May 15;557(Pt 1):3-12
references.pmid: 15034124
references.citation: J Comp Neurol. 1973 Aug;150(3):303-32
references.pmid: 4124620
references.citation: Brain Res Dev Brain Res. 2002 Dec 15;139(2):227-36
references.pmid: 12480137
references.citation: Nat Neurosci. 2004 Mar;7(3):236-43
references.pmid: 14966524
references.citation: J Neurosci. 2002 Jun 1;22(11):4487-98
references.pmid: 12040056
references.citation: Proc Natl Acad Sci U S A. 2001 May 22;98(11):6453-8
references.pmid: 11344259
references.citation: Neuron. 2002 Jan 31;33(3):357-67
references.pmid: 11832224