Katsuki H, Izumi Y, Zorumski C F
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Neurophysiol. 1997 Jun;77(6):3013-20. doi: 10.1152/jn.1997.77.6.3013.
The effects of norepinephrine (NE) and related agents on long-lasting changes in synaptic efficacy induced by several patterns of afferent stimuli were investigated in the CA1 region of rat hippocampal slices. NE (10 microM) showed little effect on the induction of long-term potentiation (LTP) triggered by theta-burst-patterned stimulation, whereas it inhibited the induction of long-term depression (LTD) triggered by 900 pulses of 1-Hz stimulation. In nontreated slices, 900 pulses of stimuli induced LTD when applied at lower frequencies (1-3 Hz), and induced LTP when applied at a higher frequency (30 Hz). NE (10 microM) caused a shift of the frequency-response relationship in the direction preferring potentiation. The effect of NE was most prominent at a stimulus frequency of 10 Hz, which induced no changes in control slices but clearly induced LTP in the presence of NE. The facilitating effect of NE on the induction of LTP by 10-Hz stimulation was blocked by the beta-adrenergic receptor antagonist timolol (50 microM), but not by the alpha receptor antagonist phentolamine (50 microM), and was mimicked by the beta-agonist isoproterenol (0.3 microM), but not by the alpha1 agonist phenylephrine (10 microM). The induction of LTD by 1-Hz stimulation was prevented by isoproterenol but not by phenylephrine, indicating that the activation of beta-receptors is responsible for these effects of NE. NE (10 microM) also prevented the reversal of LTP (depotentiation) by 900 pulses of 1-Hz stimulation delivered 30 min after LTP induction. In contrast to effects on naive (nonpotentiated) synapses, the effect of NE on previously potentiated synapses was only partially mimicked by isoproterenol, but fully mimicked by coapplication of phenylephrine and isoproterenol. In addition, the effect of NE was attenuated either by phentolamine or by timolol, indicating that activation of both alpha1 and beta-receptors is required. These results show that NE plays a modulatory role in the induction of hippocampal synaptic plasticity. Although beta-receptor activation is essential, alpha1 receptor activation is also necessary in determining effects on previously potentiated synapses.
研究了去甲肾上腺素（NE）及相关药物对大鼠海马脑片CA1区几种传入刺激模式诱导的突触效能长期变化的影响。NE（10微摩尔）对θ波爆发式刺激触发的长时程增强（LTP）诱导作用影响很小，而它抑制了1赫兹900个脉冲刺激触发的长时程抑制（LTD）。在未处理的脑片中，900个脉冲刺激在较低频率（1 - 3赫兹）施加时诱导LTD，在较高频率（30赫兹）施加时诱导LTP。NE（10微摩尔）使频率 - 反应关系向有利于增强的方向转变。NE的作用在10赫兹刺激频率时最为显著，该频率在对照脑片中不引起变化，但在有NE存在时明显诱导LTP。NE对10赫兹刺激诱导LTP的促进作用被β - 肾上腺素能受体拮抗剂噻吗洛尔（50微摩尔）阻断，但不被α受体拮抗剂酚妥拉明（50微摩尔）阻断，且被β - 激动剂异丙肾上腺素（0.3微摩尔）模拟，但不被α1激动剂去氧肾上腺素（10微摩尔）模拟。1赫兹刺激诱导的LTD被异丙肾上腺素阻止，但不被去氧肾上腺素阻止，表明β受体的激活是NE这些作用的原因。NE（10微摩尔）还阻止了LTP诱导30分钟后1赫兹900个脉冲刺激引起的LTP反转（去增强）。与对未增强（非增强）突触的作用不同，NE对先前增强突触的作用仅部分被异丙肾上腺素模拟，但被去氧肾上腺素和异丙肾上腺素共同应用完全模拟。此外，NE的作用被酚妥拉明或噻吗洛尔减弱，表明α1和β受体的激活都是必需的。这些结果表明，NE在海马突触可塑性的诱导中起调节作用。虽然β受体激活是必不可少的，但α1受体激活对于确定对先前增强突触的作用也是必要的。
