title: Role of adenylate cyclase 1 in retinofugal map development.
abstract: The development of topographic maps of the sensory periphery is sensitive to the disruption of adenylate cyclase 1 (AC1) signaling. AC1 catalyzes the production of cAMP in a Ca2+/calmodulin-dependent manner, and AC1 mutant mice (AC1−/−) have disordered visual and somatotopic maps. However, the broad expression of AC1 in the brain and the promiscuous nature of cAMP signaling have frustrated attempts to determine the underlying mechanism of AC1-dependent map development. In the mammalian visual system, the initial coarse targeting of retinal ganglion cell (RGC) projections to the superior colliculus (SC) and lateral geniculate nucleus (LGN) is guided by molecular cues, and the subsequent refinement of these crude projections occurs via an activity-dependent process that depends on spontaneous retinal waves. Here, we show that AC1−/− mice have normal retinal waves but disrupted map refinement. We demonstrate that AC1 is required for the emergence of dense and focused termination zones and elimination of inaccurately targeted collaterals at the level of individual retinofugal arbors. Conditional deletion of AC1 in the retina recapitulates map defects, indicating that the locus of map disruptions in the SC and dorsal LGN of AC1−/− mice is presynaptic. Finally, map defects in mice without AC1 and disrupted retinal waves (AC1−/−;β2−/− double KO mice) are no worse than those in mice lacking only β2−/−, but loss of AC1 occludes map recovery in β2−/− mice during the second postnatal week. These results suggest that AC1 in RGC axons mediates the development of retinotopy and eye-specific segregation in the SC and dorsal LGN.
authors.affiliation: Department of Neurobiology, Yale University, New Haven, Connecticut 06510, USA.
authors.forename: Onkar S
authors.initials: OS
authors.lastname: Dhande
authors.forename: Shivani
authors.initials: S
authors.lastname: Bhatt
authors.forename: Anastacia
authors.initials: A
authors.lastname: Anishchenko
authors.forename: Justin
authors.initials: J
authors.lastname: Elstrott
authors.forename: Takuji
authors.initials: T
authors.lastname: Iwasato
authors.forename: Eric C
authors.initials: EC
authors.lastname: Swindell
authors.forename: Hong-Ping
authors.initials: HP
authors.lastname: Xu
authors.forename: Milan
authors.initials: M
authors.lastname: Jamrich
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.forename: Marla B
authors.initials: MB
authors.lastname: Feller
authors.forename: Michael C
authors.initials: MC
authors.lastname: Crair
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001931:Brain Mapping / Q000379:methods*; D004594:Electrophysiology; D018274:Electroporation; D005829:Geniculate Bodies / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D021621:Imaging, Three-Dimensional / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013477:Superior Colliculi / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D014795:Visual Pathways / Q000166:cytology / Q000378:metabolism*
chemical_list: D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1
references.citation: J Neurosci. 2002 Jul 1;22(13):5259-64
references.pmid: 12097474
references.citation: J Neurosci. 2006 Mar 29;26(13):3594-603
references.pmid: 16571768
references.citation: Neuron. 1993 Nov;11(5):923-38
references.pmid: 8240814
references.citation: J Neurosci. 2008 Jun 4;28(23):5931-43
references.pmid: 18524897
references.citation: J Neurosci. 2011 Jan 26;31(4):1489-99
references.pmid: 21273433
references.citation: J Neurosci. 2006 Mar 8;26(10):2692-703
references.pmid: 16525048
references.citation: Genesis. 2006 Aug;44(8):361-3
references.pmid: 16850473
references.citation: Curr Opin Neurobiol. 1999 Feb;9(1):88-93
references.pmid: 10072369
references.citation: J Neurosci Methods. 2004 May 30;135(1-2):17-26
references.pmid: 15020085
references.citation: Neuron. 2007 Jun 21;54(6):961-72
references.pmid: 17582335
references.citation: Vision Res. 2004 Dec;44(28):3357-64
references.pmid: 15536003
references.citation: Neuron. 1997 Dec;19(6):1225-35
references.pmid: 9427246
references.citation: Nat Neurosci. 2006 Mar;9(3):363-71
references.pmid: 16462736
references.citation: Neuron. 1999 Nov;24(3):673-85
references.pmid: 10595518
references.citation: Curr Opin Neurobiol. 1998 Feb;8(1):139-48
references.pmid: 9568401
references.citation: J Neurosci. 1999 Nov 1;19(21):9298-305
references.pmid: 10531434
references.citation: J Neurosci. 2003 Mar 15;23(6):2228-38
references.pmid: 12657682
references.citation: Nat Neurosci. 2001 Nov;4 Suppl:1207-14
references.pmid: 11687831
references.citation: PLoS One. 2009 Nov 17;4(11):e7877
references.pmid: 19924297
references.citation: J Neurosci. 2003 Apr 1;23(7):2851-60
references.pmid: 12684472
references.citation: Neuron. 2003 Dec 18;40(6):1147-60
references.pmid: 14687549
references.citation: Science. 1996 May 24;272(5265):1182-7
references.pmid: 8638165
references.citation: J Hered. 1986 Mar-Apr;77(2):66-82
references.pmid: 3711643
references.citation: Eur J Neurosci. 2006 Dec;24(12):3401-14
references.pmid: 17229090
references.citation: Neuron. 1998 Feb;20(2):235-43
references.pmid: 9491985
references.citation: J Neurosci. 2005 Jul 20;25(29):6929-38
references.pmid: 16033903
references.citation: J Neurosci. 2006 Dec 13;26(50):12873-84
references.pmid: 17167078
references.citation: Neuron. 2005 Dec 8;48(5):797-809
references.pmid: 16337917
references.citation: Nature. 2005 Apr 21;434(7036):1022-6
references.pmid: 15846347
references.citation: J Neurosci. 1998 Jun 1;18(11):4155-65
references.pmid: 9592095
references.citation: Neuron. 2000 Mar;25(3):563-74
references.pmid: 10774725
references.citation: Prog Brain Res. 2001;131:599-613
references.pmid: 11420974
references.citation: Prog Neurobiol. 2005 Jul;76(4):213-35
references.pmid: 16280194
references.citation: Nat Protoc. 2008;3(6):1101-8
references.pmid: 18546601
references.citation: Neuron. 2011 Jun 23;70(6):1115-27
references.pmid: 21689598
references.citation: Genes Dev. 2000 Jun 1;14(11):1377-89
references.pmid: 10837030
references.citation: Nat Neurosci. 2003 Sep;6(9):939-47
references.pmid: 12897788
references.citation: Science. 2003 Jul 4;301(5629):66-70
references.pmid: 12843386
references.citation: J Neurosci. 2010 Aug 11;30(32):10939-51
references.pmid: 20702722
references.citation: Nat Neurosci. 2007 Mar;10(3):340-7
references.pmid: 17259982
references.citation: J Neurosci. 2011 Mar 2;31(9):3384-99
references.pmid: 21368050
references.citation: Neuron. 2010 Oct 6;68(1):32-44
references.pmid: 20920789
references.citation: Curr Opin Neurobiol. 2011 Apr;21(2):228-37
references.pmid: 21558027
references.citation: J Neurosci. 2006 Dec 6;26(49):12807-15
references.pmid: 17151284
references.citation: Annu Rev Neurosci. 2005;28:327-55
references.pmid: 16022599
references.citation: FEBS Lett. 2000 Mar 31;470(3):263-8
references.pmid: 10745079
references.citation: Neuron. 2003 Dec 18;40(6):1161-72
references.pmid: 14687550
references.citation: Nat Neurosci. 2005 Jan;8(1):72-8
references.pmid: 15608630
references.citation: J Neurosci. 2006 Jan 18;26(3):862-72
references.pmid: 16421306
references.citation: Neuron. 2009 Apr 30;62(2):230-41
references.pmid: 19409268
references.citation: Nat Genet. 1999 Jan;21(1):70-1
references.pmid: 9916792
references.citation: J Comp Neurol. 2005 Jun 6;486(3):281-94
references.pmid: 15844169
references.citation: Science. 1991 May 17;252(5008):939-43
references.pmid: 2035024
references.citation: J Neurosci. 2006 Mar 29;26(13):3604-14
references.pmid: 16571769
references.citation: Nat Genet. 1998 Jul;19(3):289-91
references.pmid: 9662407
references.citation: Proc Natl Acad Sci U S A. 2001 May 22;98(11):6453-8
references.pmid: 11344259
references.citation: Annu Rev Neurosci. 2008;31:479-509
references.pmid: 18558864
references.citation: Neuron. 2002 Jan 31;33(3):357-67
references.pmid: 11832224
references.citation: J Neurosci. 2010 Mar 17;30(11):4110-9
references.pmid: 20237281