期刊
MOLECULAR PSYCHIATRY
卷 18, 期 9, 页码 993-1005出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2012.123
关键词
glucocorticoid; stress; hippocampus; neural stem cell; dentate gyrus; adult neurogenesis
资金
- Netherlands Technology Foundation (STW)
- Applied Science Division of the Netherlands Scientific Organization
- Technology Program of the Netherlands Ministry of Economic affairs [LFA6332]
- Center for Medical System Biology, Leiden, The Netherlands
- HersenStichting Nederland
- ISAO
- Netherlands Organization for Scientific Research (NOW) [VIDI H64.09.016]
Glucocorticoids (GCs) secreted after stress reduce adult hippocampal neurogenesis, a process that has been implicated in cognitive aspects of psychopathology, amongst others. Yet, the exact role of the GC receptor (GR), a key mediator of GC action, in regulating adult neurogenesis is largely unknown. Here, we show that GR knockdown, selectively in newborn cells of the hippocampal neurogenic niche, accelerates their neuronal differentiation and migration. Strikingly, GR knockdown induced ectopic positioning of a subset of the new granule cells, altered their dendritic complexity and increased their number of mature dendritic spines and mossy fiber boutons. Consistent with the increase in synaptic contacts, cells with GR knockdown exhibit increased basal excitability parallel to impaired contextual freezing during fear conditioning. Together, our data demonstrate a key role for the GR in newborn hippocampal cells in mediating their synaptic connectivity and structural as well as functional integration into mature hippocampal circuits involved in fear memory consolidation.
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