title: Development of hippocampal mossy fiber synaptic outputs by new neurons in the adult brain.
abstract: New neurons are continuously generated in restricted regions of the adult mammalian brain. Although these adult-born neurons have been shown to receive synaptic inputs, little is known about their synaptic outputs. Using retrovirus-mediated birth-dating and labeling in combination with serial section electron microscopic reconstruction, we report that mossy fiber en passant boutons of adult-born dentate granule cells form initial synaptic contacts with CA3 pyramidal cells within 2 weeks after their birth and reach morphologic maturity within 8 weeks in the adult hippocampus. Knockdown of Disrupted-in-Schizophrenia-1 (DISC1) in newborn granule cells leads to defects in axonal targeting and development of synaptic outputs in the adult brain. Together with previous reports of synaptic inputs, these results demonstrate that adult-born neurons are fully integrated into the existing neuronal circuitry. Our results also indicate a role for DISC1 in presynaptic development and may have implications for the etiology of schizophrenia and related mental disorders.
authors.affiliation: Center for Neuroscience, University of California, Davis, CA 95618, USA.
authors.forename: Regina L
authors.initials: RL
authors.lastname: Faulkner
authors.forename: Mi-Hyeon
authors.initials: MH
authors.lastname: Jang
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Duan
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Sailor
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Shaoyu
authors.initials: S
authors.lastname: Ge
authors.forename: Edward G
authors.initials: EG
authors.lastname: Jones
authors.forename: Guo-li
authors.initials: GL
authors.lastname: Ming
authors.forename: Hongjun
authors.initials: H
authors.lastname: Song
authors.forename: Hwai-Jong
authors.initials: HJ
authors.lastname: Cheng
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D019599:Mossy Fibers, Hippocampal / Q000254:growth & development* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D034622:RNA Interference; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure
chemical_list: C498794:Disc1 protein, mouse; D009419:Nerve Tissue Proteins
references.citation: J Virol. 1994 Jan;68(1):510-6
references.pmid: 8254763
references.citation: Neuron. 2006 Oct 5;52(1):139-53
references.pmid: 17015232
references.citation: Nat Rev Neurosci. 2006 Mar;7(3):179-93
references.pmid: 16495940
references.citation: Mol Psychiatry. 2007 Jan;12(1):74-86
references.pmid: 17043677
references.citation: Nat Neurosci. 2003 May;6(5):507-18
references.pmid: 12704391
references.citation: Nat Cell Biol. 2005 Dec;7(12):1167-78
references.pmid: 16299498
references.citation: J Neurosci. 2005 Nov 2;25(44):10074-86
references.pmid: 16267214
references.citation: J Comp Neurol. 2003 Nov 24;466(4):457-67
references.pmid: 14566942
references.citation: J Comp Neurol. 1981 Jan 1;195(1):51-86
references.pmid: 7204652
references.citation: Neurosurg Clin N Am. 2007 Jan;18(1):105-13, x
references.pmid: 17244558
references.citation: J Neurosci. 1998 May 1;18(9):3386-403
references.pmid: 9547246
references.citation: J Histochem Cytochem. 1983 May;31(5):669-74
references.pmid: 6341457
references.citation: Curr Opin Neurobiol. 2007 Feb;17(1):95-102
references.pmid: 17258902
references.citation: Mol Psychiatry. 2007 Oct;12(10):897-9
references.pmid: 17895924
references.citation: Synapse. 2005 Jul;57(1):47-55
references.pmid: 15858835
references.citation: Synapse. 2007 Aug;61(8):615-21
references.pmid: 17476682
references.citation: Cell. 2007 Sep 21;130(6):1146-58
references.pmid: 17825401
references.citation: Nature. 2006 Feb 2;439(7076):589-93
references.pmid: 16341203
references.citation: Nat Neurosci. 2007 Jun;10(6):727-34
references.pmid: 17486101
references.citation: J Comp Neurol. 1999 Apr 19;406(4):449-60
references.pmid: 10205022
references.citation: Annu Rev Neurosci. 2005;28:223-50
references.pmid: 16022595
references.citation: J Neurosci. 2006 Feb 22;26(8):2326-34
references.pmid: 16495460
references.citation: J Neurosci. 2007 Jan 3;27(1):15-26
references.pmid: 17202468
references.citation: Proc Natl Acad Sci U S A. 2008 May 13;105(19):7076-81
references.pmid: 18458327
references.citation: Nature. 2002 Feb 28;415(6875):1030-4
references.pmid: 11875571
references.citation: J Neurosci. 2005 Oct 5;25(40):9124-34
references.pmid: 16207871
references.citation: Curr Opin Neurobiol. 2008 Feb;18(1):108-15
references.pmid: 18514504
references.citation: J Comp Neurol. 1999 Oct 11;413(1):146-54
references.pmid: 10464376
references.citation: Cell. 2008 Feb 22;132(4):645-60
references.pmid: 18295581
references.citation: Biol Psychiatry. 2006 Jun 15;59(12):1189-97
references.pmid: 16797264
references.citation: Neuroscience. 2004;124(1):3-10
references.pmid: 14960334
references.citation: J Neurosci. 2006 Jan 4;26(1):3-11
references.pmid: 16399667
references.citation: J Neurosci. 2007 Sep 26;27(39):10434-44
references.pmid: 17898215
references.citation: J Neurosci. 2007 Jan 3;27(1):4-14
references.pmid: 17202467