Intra-amygdala injections of CREB antisense impair inhibitory avoidance memory: Role of norepinephrine and acetylcholine
Intra-amygdala injections of CREB antisense impair inhibitory avoidance memory: Role of norepinephrine and acetylcholine
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DOI：
10.1101/lm.904308
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发表时间：
2008-09-01
影响因子：
2
通讯作者：
Gold, Paul E.
中科院分区：
文献类型：
--
作者：
Canal, Clinton E.;Chang, Qing;Gold, Paul E.
在训练前将CREB反义注入杏仁核会损害厌恶任务的记忆，这表明反义可能会干扰CREB介导的基因转录和蛋白质合成，这些基因转录和蛋白质合成对杏仁核内新记忆的形成至关重要。然而，杏仁核似乎也通过杏仁核内释放去甲肾上腺素和乙酰胆碱等机制来调节大脑分布部位的记忆形成。因此，CREB反义注射可能通过干扰记忆的调节机制而不是存储机制来影响记忆。在本实验中，大鼠接受双侧杏仁核内注入CREB反义（2 nmol/1 μ L）6小时前抑制性回避训练。在体内微透析样品收集从右杏仁核之前，期间和之后的培训。训练后48小时测试CREB反义产生健忘症。此外，CREB反义输注抑制了杏仁核中与训练相关的去甲肾上腺素的释放，并在较小程度上抑制了乙酰胆碱的释放。此外，杏仁核内注射β-肾上腺素能受体激动剂克伦特罗后立即训练衰减记忆障碍引起的杏仁核内注射CREB反义。这些研究结果表明，杏仁核内的CREB反义治疗可能会影响参与调制的记忆，部分通过干扰杏仁核中的去甲肾上腺素和乙酰胆碱神经传递的过程。
Infusions of CREB antisense into the amygdala prior to training impair memory for aversive tasks, suggesting that the antisense may interfere with CRE-mediated gene transcription and protein synthesis important for the formation of new memories within the amygdala. However, the amygdala also appears to modulate memory formation in distributed brain sites, through mechanisms that include the release of norepinephrine and acetylcholine within the amygdala. Thus, CREB antisense injections may affect memory by interfering with mechanisms of modulation, rather than storage, of memory. In the present experiment, rats received bilateral intra-amygdala infusions of CREB antisense (2 nmol/1 mu L) 6 h prior to inhibitory avoidance training. In vivo microdialysis samples were collected from the right amygdala before, during, and following training. CREB antisense produced amnesia tested at 48 h after training. In addition, CREB antisense infusions dampened the training-related release of norepinephrine, and to a lesser extent of acetylcholine, in the amygdala. Furthermore, intra-amygdala infusions of the beta-adrenergic receptor agonist clenbuterol administered immediately after training attenuated memory impairments induced by intra-amygdala injections of CREB antisense. These findings suggest that intra-amygdala treatment with CREB antisense may affect processes involved in modulation of memory in part through interference with norepinephrine and acetylcholine neurotransmission in the amygdala.