期刊
JOURNAL OF NEUROSCIENCE
卷 36, 期 18, 页码 4940-4958出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3876-15.2016
关键词
arborization; learning; memory; neurogenesis; TRIM9
资金
- National Institutes of Health [R01-GM108970, F31-NS087837, F31-NS093917, U54-HD079124, MH106939]
- Brain and Behavioral Foundation
- American Heart Association
- Whitehall Foundation
- University of North Carolina Department of Pharmacology startup Fund
- Lineberger Comprehensive Cancer Center startup Funds
During hippocampal development, newly born neurons migrate to appropriate destinations, extend axons, and ramify dendritic arbors to establish functional circuitry. These developmental stages are recapitulated in the dentate gyrus of the adult hippocampus, where neurons are continuously generated and subsequently incorporate into existing, local circuitry. Here we demonstrate that the E3 ubiquitin ligase TRIM9 regulates these developmental stages in embryonic and adult-born mouse hippocampal neurons in vitro and in vivo. Embryonic hippocampal and adult-born dentate granule neurons lacking Trim9 exhibit several morphological defects, including excessive dendritic arborization. Although gross anatomy of the hippocampus was not detectably altered by Trim9 deletion, a significant number of Trim9(-/-) adult-born dentate neurons localized inappropriately. These morphological and localization defects of hippocampal neurons in Trim9(-/-) mice were associated with extreme deficits in spatial learning and memory, suggesting that TRIM9-directed neuronal morphogenesis may be involved in hippocampal-dependent behaviors.
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