Delayed Noradrenergic Activation in the Dorsal Hippocampus Promotes the Long-Term Persistence of Extinguished Fear
| العنوان: | Delayed Noradrenergic Activation in the Dorsal Hippocampus Promotes the Long-Term Persistence of Extinguished Fear |
|---|---|
| المؤلفون: | Ning Chai, Lin Lu, Ji-Shi Wang, Xue-Yi Wang, Chang Yang, Yan-Xue Xue, Wei Yan, Jian-Feng Liu, Yi-Xiao Luo, Zeng-Bo Ding, Yanping Bao, Hai-Shui Shi, Hui-Min Wang, Shi-Qiu Meng |
| المصدر: | Neuropsychopharmacology. 39:1933-1945 |
| بيانات النشر: | Springer Science and Business Media LLC, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Male, Memory, Long-Term, Motor Activity, Hippocampal formation, CREB, Extinction, Psychological, Rats, Sprague-Dawley, Norepinephrine, chemistry.chemical_compound, Conditioning, Psychological, Receptors, Adrenergic, beta, medicine, Animals, Cyclic adenosine monophosphate, Phosphorylation, Protein kinase A, CA1 Region, Hippocampal, Anisomycin, Pharmacology, biology, Antagonist, Fear, social sciences, musculoskeletal system, medicine.disease, humanities, Rats, Cell biology, Psychiatry and Mental health, chemistry, Protein Biosynthesis, Extinction (neurology), biology.protein, Original Article, Signal transduction, Neuroscience, geographic locations, psychological phenomena and processes, Signal Transduction |
| الوصف: | Fear extinction has been extensively studied, but little is known about the molecular processes that underlie the persistence of extinction long-term memory (LTM). We found that microinfusion of norepinephrine (NE) into the CA1 area of the dorsal hippocampus during the early phase (0 h) after extinction enhanced extinction LTM at 2 and 14 days after extinction. Intra-CA1 infusion of NE during the late phase (12 h) after extinction selectively promoted extinction LTM at 14 days after extinction that was blocked by the β-receptor antagonist propranolol, protein kinase A (PKA) inhibitor Rp-cAMPS, and protein synthesis inhibitors anisomycin and emetine. The phosphorylation levels of PKA, cyclic adenosine monophosphate response element-binding protein (CREB), GluR1, and the membrane GluR1 level were increased by NE during the late phase after extinction that was also blocked by propranolol and Rp-cAMPS. These results suggest that the enhancement of extinction LTM persistence induced by NE requires the activation of the β-receptor/PKA/CREB signaling pathway and membrane GluR1 trafficking. Moreover, extinction increased the phosphorylation levels of Erk1/2, CREB, and GluR1, and the membrane GluR1 level during the late phase, and anisomycin/emetine alone disrupted the persistence of extinction LTM, indicating that the persistence of extinction LTM requires late-phase protein synthesis in the CA1. Propranolol and Rp-cAMPS did not completely disrupt the persistence of extinction LTM, suggesting that another β-receptor/PKA-independent mechanism underlies the persistence of extinction LTM. Altogether, our results showed that enhancing hippocampal noradrenergic activity during the late phase after extinction selectively promotes the persistence of extinction LTM. |
| تدمد: | 1740-634X 0893-133X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::86612993e1582b5109a65acc56f69575 https://doi.org/10.1038/npp.2014.42 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....86612993e1582b5109a65acc56f69575 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1740634X 0893133X |
|---|