Development of hippocampal mossy fiber synaptic outputs by new neurons in the adult brain.
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.
Faulkner
Regina L
RL
Center for Neuroscience, University of California, Davis, CA 95618, USA.
Jang
Mi-Hyeon
MH
Liu
Xiao-Bo
XB
Duan
Xin
X
Sailor
Kurt A
KA
Kim
Ju Young
JY
Ge
Shaoyu
S
Jones
Edward G
EG
Ming
Guo-li
GL
Song
Hongjun
H
Cheng
Hwai-Jong
HJ
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
C498794:Disc1 protein, mouse; D009419:Nerve Tissue Proteins
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