Leão Ricardo M, Von Gersdorff Henrique
The Vollum Institute, Oregon Health and Science University, Portland, Oregon 97201-3098, USA.
J Neurophysiol. 2002 May;87(5):2297-306. doi: 10.1152/jn.2002.87.5.2297.
The mammalian auditory brain stem receives profuse adrenergic innervation, whose function is poorly understood. Here we investigate, during postnatal development, the effect of noradrenaline (NA) at the calyx of Held synapse in the rat medial nucleus of the trapezoid body (MNTB). We observed that NA inhibits the large glutamatergic EPSC, evoked by afferent fiber stimulation, in a dose-dependent manner. The inhibition was maximal (approximately 48%) at the concentration of 2 microM. It was antagonized by yohimbine and mimicked by the alpha2-adrenergic specific agonist UK14304. Both AMPA and NMDA receptor-mediated EPSCs were inhibited in parallel by NA, suggesting a presynaptic effect. Presynaptic recordings showed that NA inhibits the action potential (AP) generated Ca current by about 20%; however, NA did not significantly affect the presynaptic AP waveform. We thus conclude that the calyx of Held presynaptic terminal expresses alpha2-adrenergic receptors that inhibit its Ca current and thus glutamate release. Noradrenaline was effective in all cells tested from postnatal days 6 to 7 (P6-P7), and thereafter the number of responsive cells diminished, although half of the P14 cells tested still had EPSCs that were inhibited by NA. By contrast, activation by L-2-amino-5-phosphonovaleric acid-sensitive metabotropic glutamate receptors strongly inhibited the EPSCs of all cells tested from P6 to P14. The effect of NA on postsynaptic action potential firing was dependent on the stimulus frequency. At 10 Hz, NA had no effect on firing probability; however, NA helped MNTB cells fire more action potentials during a 100-Hz train of stimuli, even though it did not increase the steady-state depressed EPSC, because it produced a smaller N-methyl-D-aspartate (NMDA) receptor-activated depolarizing plateau. We therefore suggest that the reduction by NA of the first few EPSCs in a train leads to a smaller NMDA depolarizing plateau and thus to increased firing probability at 100 Hz in young synapses. Surprisingly, the inhibition of glutamate release by NA can thus actually increase the excitability of MNTB neurons during early postnatal development.
哺乳动物的听觉脑干接受丰富的肾上腺素能神经支配，但其功能尚不清楚。在此，我们研究了在出生后发育过程中，去甲肾上腺素（NA）对大鼠梯形体内侧核（MNTB）中Held壶腹突触的影响。我们观察到，NA以剂量依赖的方式抑制传入纤维刺激诱发的大的谷氨酸能兴奋性突触后电流（EPSC）。在2 microM的浓度下，抑制作用最大（约48%）。它被育亨宾拮抗，被α2-肾上腺素能特异性激动剂UK14304模拟。NA同时平行抑制AMPA和NMDA受体介导的EPSC，表明是突触前效应。突触前记录显示，NA将动作电位（AP）产生的钙电流抑制约20%；然而，NA对突触前AP波形没有显著影响。因此，我们得出结论，Held壶腹突触前终末表达α2-肾上腺素能受体，其抑制钙电流，从而抑制谷氨酸释放。去甲肾上腺素在出生后第6至7天（P6 - P7）测试的所有细胞中均有效，此后反应性细胞数量减少，尽管在P14测试的细胞中有一半的EPSC仍被NA抑制。相比之下，L - 2 - 氨基 - 5 - 磷酸戊酸敏感的代谢型谷氨酸受体激活强烈抑制从P6到P14测试的所有细胞的EPSC。NA对突触后动作电位发放的影响取决于刺激频率。在10 Hz时，NA对发放概率没有影响；然而，在100 Hz的刺激序列中，NA帮助MNTB细胞产生更多动作电位，尽管它没有增加稳态抑制的EPSC，因为它产生了较小的N - 甲基 - D - 天冬氨酸（NMDA）受体激活的去极化平台。因此，我们认为，NA对一串刺激中最初几个EPSC的减少导致较小的NMDA去极化平台，从而导致年轻突触在100 Hz时发放概率增加。令人惊讶的是，在出生后早期发育过程中，NA对谷氨酸释放的抑制实际上可以增加MNTB神经元的兴奋性。
