Murchison Charles F, Zhang Xiao-Yan, Zhang Wei-Ping, Ouyang Ming, Lee Anee, Thomas Steven A
Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell. 2004 Apr 2;117(1):131-43. doi: 10.1016/s0092-8674(04)00259-4.
A role for norepinephrine in learning and memory has been elusive and controversial. A longstanding hypothesis states that the adrenergic nervous system mediates enhanced memory consolidation of emotional events. We tested this hypothesis in several learning tasks using mutant mice conditionally lacking norepinephrine and epinephrine, as well as control mice and rats treated with adrenergic receptor agonists and antagonists. We find that adrenergic signaling is critical for the retrieval of intermediate-term contextual and spatial memories, but is not necessary for the retrieval or consolidation of emotional memories in general. The role of norepinephrine in retrieval requires signaling through the beta(1)-adrenergic receptor in the hippocampus. The results demonstrate that mechanisms of memory retrieval can vary over time and can be different from those required for acquisition or consolidation. These findings may be relevant to symptoms in several neuropsychiatric disorders as well as the treatment of cardiac failure with beta blockers.
去甲肾上腺素在学习和记忆中的作用一直难以捉摸且存在争议。一个长期存在的假说是，肾上腺素能神经系统介导情绪事件增强的记忆巩固。我们使用有条件缺乏去甲肾上腺素和肾上腺素的突变小鼠，以及用肾上腺素能受体激动剂和拮抗剂处理的对照小鼠和大鼠，在多个学习任务中测试了这一假说。我们发现，肾上腺素能信号对于中期情境和空间记忆的提取至关重要，但一般而言对于情绪记忆的提取或巩固并非必要。去甲肾上腺素在提取中的作用需要通过海马体中的β(1)-肾上腺素能受体进行信号传导。结果表明，记忆提取机制会随时间变化，且可能与获取或巩固所需的机制不同。这些发现可能与几种神经精神疾病的症状以及用β受体阻滞剂治疗心力衰竭有关。
