期刊
ENEURO
卷 7, 期 1, 页码 -出版社
SOC NEUROSCIENCE
DOI: 10.1523/ENEURO.0303-19.2019
关键词
elimination; hippocampal neurons; kinase; optogenetics; spine; stress
资金
- Academy of Finland [135090, 310583 EU FP7 ITN 608346]
- Molecular Biology Graduate School at Abo Akademi University
- Academy of Finland (AKA) [135090, 135090] Funding Source: Academy of Finland (AKA)
In this study, we use an optogenetic inhibitor of c-Jun NH2-terminal kinase (JNK) in dendritic spine subcompartments of rat hippocampal neurons. We show that JNK inhibition exerts rapid (within seconds) reorganization of actin in the spine-head. Using real-time Forster resonance energy transfer (FRET) to measure JNK activity, we find that either excitotoxic insult (NMDA) or endocrine stress (corticosterone), activate spine-head JNK causing internalization of AMPARs and spine retraction. Both events are prevented upon optogenetic inhibition of JNK, and rescued by JNK inhibition even 2 h after insult. Moreover, we identify that the fast-acting anti-depressant ketamine reduces JNK activity in hippocampal neurons suggesting that JNK inhibition may be a downstream mediator of its anti-depressant effect. In conclusion, we show that JNK activation plays a role in triggering spine elimination by NMDA or corticosterone stress, whereas inhibition of JNK facilitates regrowth of spines even in the continued presence of glucocorticoid. This identifies that JNK acts locally in the spine-head to promote AMPAR internalization and spine shrinkage following stress, and reveals a protective function for JNK inhibition in preventing spine regression.
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