海马脑区去甲肾上腺素β-受体在学习和记忆中的作用

【作者】 季今朝；

【导师】 李葆明；

【作者基本信息】 中国科学院研究生院（上海生命科学研究院） ， 神经生物学， 2003， 博士

【摘要】 第一部分 大鼠海马CA1区β-受体参与长时程增强和空间 学习在离体海马脑片上，激活CA1区(-肾上腺素能受体（β-受体）易化这一区域突触传递的长时程增强（LTP）。然而，在体情况下，CA1区β-受体是否参与LTP，是否参与海马依赖性的学习和记忆，尚无实验证据。为此，我们观察了β-受体激动剂异丙肾上腺素（isoproterenol）或拮抗剂心得安(propranolol)对在体CA1区LTP的调控作用以及对大鼠在Morris水迷宫中空间学习的影响。正常情况下对突触传递效能仅有微小调制作用的10Hz的(节律刺激（每串150个脉冲，1串），在CA1区局部给予L-异丙肾上腺素后，显著地诱导出LTP，这一效应可被DL-心得安所阻断；相反，正常情况下对突触传递强度有显著调制作用的5Hz的(节律刺激（每串150个脉冲，3串），在CA1区局部给予DL-心得安后，所诱导出的LTP被显著压抑。对应的，训练前20分钟在CA1 区注射DL-心得安，大鼠在水迷宫中的学习速度显著慢于对照组，训练后24小时的空间记忆保持也相应地差。以上结果提示，β-受体参与对在体海马CA1区突触可塑性的调控，且对空间学习重要。本工作首次在在体条件下，通过(节律刺激诱导出了CA1区的LTP，并对其β-受体的调控作用进行了观察，为海马CA1区β-受体参与空间学习首次提供了行为学证据。关键词：β-受体, 长时程增强, CA1区, 海马, 空间学习，大鼠更多还原

【Abstract】 Part I Involvement of (β-adrenoceptors in hippocampal CA1 region in in vivo long-term potentiation and spatial learning in rats Activation of (β-adrenoceptors in area CA1 of the hippocampus facilitates in vitro long-term potentiation (LTP) in this region. However, it is unclear if in vivo LTP in area CA1 and hippocampus-dependent learning are subjected to (-adrenergic regulation. To address this question, we investigated the effects of the (-adrenergic agonist L-isoproterenol or antagonist DL-propranolol on in vivo LTP of area CA1 and spatial learning in Morris water maze. In the presence of L-isoproterenol (through local infusion into area CA1), the theta-pulse stimulation with the parameter of 10 Hz, 150 pulses/train, 1 train, a frequency weakly modifying synaptic strength, induced a robust LTP, and this effect was blocked when DL-propranolol was co-administered. By contrast, the theta-pulse stimulation with the parameter of 5 Hz, 150 pulses/train, 3 train, a frequency strongly modifying synaptic strength, induced a significantly smaller LTP when DL-propranolol was administered into area CA1. Accordingly, DL-propranolol impaired rat’s spatial learning in the water maze when infused into area CA1 20min pretraining. Compared with control rats, the DL-propranolol-treated rats showed significantly slower learning in the water maze and subsequently exhibited poor memory retention at 24-hr<WP=10>test. These results suggest that β-adrenoceptors in area CA1 are involved in regulating in vivo synaptic plasticity of this area and are important for spatial learning. The present study was the first work where theta-pulse-stimulation-induced LTP was recorded in area CA1 in vivo and its (-adrenergic regulation was examined, and provided the first behavioral evidence that (-adreneoceptors in area CA1 plays an important role in spatial learning.Key words:β-adrenoceptors, long-term potentiation, CA1, hippocampus, spatial learning, rat更多还原