Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 105, Issue 37, Pages 14157-14162Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0806658105
Keywords
adult neurogenesis; synaptogenesis; DISC1; hippocampus; axon guidance
Categories
Funding
- National Institutes of Health [NS047344, AG024984, MH084018, NS048271, HD045757]
- McKnight Scholar Award
- Robert Packard Center for ALS Research
- Muscular Dystrophy Association
- Rett Syndrome Research Foundation
- Simons Foundation
- Klingenstein Fellowship Award in the Neurosciences
- March of Dimes Foundation
- Adelson Medical Research Foundation
- Whitehall Foundation
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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.
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