Mouradian R D, Sessler F M, Waterhouse B D
Department of Physiology and Biophysics, Hahnemann University, Philadelphia, PA 19102-1192.
Brain Res. 1991 Apr 12;546(1):83-95. doi: 10.1016/0006-8993(91)91162-t.
Considerable evidence from intact, anesthetized preparations suggests that norepinephrine (NE) can modulate the efficacy of synaptic transmission within local circuits of the mammalian neocortex; i.e. both iontophoretic application of NE and activation of the coeruleocortical pathway are capable of facilitating cortical neuronal responses to non-noradrenergic synaptic inputs and putative transmitter agents. In the present study, the effects of NE on somatosensory cortical neuronal responses to putative excitatory transmitters were characterized using in vitro tissue slice preparations. Somatosensory unit responses to iontophoretic pulses of acetylcholine (ACh) or glutamate (Glu) (10-60 nA; 5-25 s duration) were examined before, during and after a period of continuous NE (1-35 nA; 4-25 min duration) microiontophoresis. Quantitative analysis of per-event histograms indicated that both Glu- and ACh-evoked excitatory discharges were routinely (Glu 94%, n = 54; ACh 67%, n = 9) potentiated above control levels during NE administration. In 8 cells, NE revealed robust excitatory discharges to otherwise subthreshold iontophoretic doses of Glu. The alpha-specific agonist, phenylephrine, mimicked (n = 3), NE-induced potentiation of Glu-evoked discharges whereas the alpha antagonist phentolamine blocked (n = 5) enhancement of these responses. Moreover, activation of protein kinase C by iontophoretic application of phorbol 12,13-diacetate (5-15 nA, n = 4) mimicked the potentiating actions of NE on Glu-evoked excitatory responses. Results from other experiments further indicated that these facilitating actions of NE on Glu-evoked responses do not involve beta receptor activation or intracellular increases in cyclic AMP. In summary, these results demonstrate that NE can facilitate cortical neuronal responses to threshold and subthreshold level applications of putative excitatory transmitter agents. Moreover, it appears that, unlike noradrenergic facilitating influences on GABA-induced inhibition, these actions are mediated by an alpha adrenoceptor mechanism which may be linked to intracellular activation of protein kinase C. Overall, these findings reinforce the idea that noradrenergic modulatory actions on excitatory and inhibitory neuronal responses may involve the activation of separate receptor-linked second messenger systems.
来自完整的、麻醉状态下的实验标本的大量证据表明，去甲肾上腺素（NE）能够调节哺乳动物新皮质局部回路中突触传递的效能；也就是说，离子电渗法施加NE以及激活蓝斑皮质通路都能够促进皮质神经元对非去甲肾上腺素能突触输入和假定递质的反应。在本研究中，利用体外组织切片标本对NE对体感皮质神经元对假定兴奋性递质的反应的影响进行了表征。在持续NE（1 - 35 nA；持续4 - 25分钟）微离子电渗期间及之后，检测了体感单位对乙酰胆碱（ACh）或谷氨酸（Glu）（10 - 60 nA；持续5 - 25秒）离子电渗脉冲的反应。对逐个事件直方图的定量分析表明，在给予NE期间，Glu和ACh诱发的兴奋性放电通常（Glu为94%，n = 54；ACh为67%，n = 9）增强至对照水平以上。在8个细胞中，NE对原本低于阈值的离子电渗剂量的Glu表现出强烈的兴奋性放电。α特异性激动剂去氧肾上腺素模拟了（n = 3）NE诱导的Glu诱发放电的增强，而α拮抗剂酚妥拉明阻断了（n = 5）这些反应的增强。此外，通过离子电渗法施加佛波醇12,13 - 二乙酸酯（5 - 15 nA，n = 4）激活蛋白激酶C模拟了NE对Glu诱发的兴奋性反应的增强作用。其他实验结果进一步表明，NE对Glu诱发反应的这些促进作用不涉及β受体激活或细胞内环磷酸腺苷的增加。总之，这些结果表明NE能够促进皮质神经元对假定兴奋性递质的阈值和低于阈值水平应用的反应。此外，似乎与去甲肾上腺素能对GABA诱导的抑制的促进作用不同，这些作用是由α肾上腺素能受体机制介导的，该机制可能与蛋白激酶C细胞内激活有关。总体而言，这些发现强化了这样一种观点，即去甲肾上腺素能对兴奋性和抑制性神经元反应的调节作用可能涉及激活不同的受体相关第二信使系统。
