Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90050-170 Porto Alegre, RS, Brazil.
Neurobiol Learn Mem. 2012 Jan;97(1):105-12. doi: 10.1016/j.nlm.2011.10.002. Epub 2011 Oct 19.
Mammalian target of rapamycin (mTOR), a central regulator of protein synthesis in neurons, has been implicated in synaptic plasticity and memory. Here we show that mTOR inhibition by rapamycin in the basolateral amygdala (BLA) or dorsal hippocampus (DH) impairs both formation and reconsolidation of memory for inhibitory avoidance (IA) in rats. Male Wistar rats received bilateral infusions of vehicle or rapamycin into the BLA or DH before or after IA training or retrieval. Memory retention was tested at different time points after drug infusion. Rapamycin impaired long-term IA retention when given before or immediately after training or retrieval into the BLA. When infused into the DH, rapamycin produced memory impairment when given before training or immediately after retrieval. The impairing effects of post-retrieval rapamycin required memory retrieval and were not reversed by a reminder shock. The results provide the first evidence that mTOR in the BLA and DH might play a role in IA memory reconsolidation.
哺乳动物雷帕霉素靶蛋白(mTOR)是神经元中蛋白质合成的中枢调节剂,它与突触可塑性和记忆有关。在这里,我们表明,雷帕霉素在基底外侧杏仁核(BLA)或背侧海马(DH)中的抑制作用会损害大鼠抑制性回避(IA)的形成和再巩固。雄性 Wistar 大鼠在 IA 训练或检索之前或之后,通过双侧输注载体或雷帕霉素到 BLA 或 DH。在药物输注后不同时间点测试记忆保留情况。雷帕霉素在 BLA 中给药前或训练或检索后立即给药会损害长期 IA 保留。当注入 DH 时,雷帕霉素在训练前或检索后立即给药会导致记忆损伤。检索后雷帕霉素的损伤作用需要记忆检索,并且不能通过提醒性休克逆转。结果首次提供了证据,表明 BLA 和 DH 中的 mTOR 可能在 IA 记忆再巩固中发挥作用。