Development of hippocampal mossy fiber synaptic outputs by new neurons in the adult brain

Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):14157-62. doi: 10.1073/pnas.0806658105. Epub 2008 Sep 9.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Animals, Newborn
  • Female
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron
  • Mossy Fibers, Hippocampal / growth & development*
  • Mossy Fibers, Hippocampal / ultrastructure
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / cytology*
  • Neurons / metabolism
  • RNA Interference
  • Synapses / physiology*
  • Synapses / ultrastructure

Substances

  • Disc1 protein, mouse
  • Nerve Tissue Proteins