Functional roles of co-transmitters in brainsten cholinergic neurons

紧密聚集在脑干背外侧被盖核（LDT）内的胆碱能神经元以一氧化氮（NO）和/或P物质（SP）为共递质。本研究考察了这些共递质是否从轴突末端或变异处释放，以及它们对突触后靶点的影响。在之前的研究中，我们已经证明LDT刺激产生了丘脑中继神经元的兴奋，这些神经元接受了胆碱能神经元的直接投射。我们用激光多普勒血流仪检查了被聚氨酯麻醉的大鼠，同样的LDT刺激如何影响丘脑的脑血流量，因为共递质对血管有很强的作用。在LDT刺激开始后的几秒钟内观察到血流的增加，并在刺激后持续约1分钟。服用东莨菪碱（一种毒蕈碱拮抗剂）后，这种增加有所减少，但治疗并没有完全阻断它。使用盐野氏研究实验室（Shionogi Research Laboratories）开发的对NO特异敏感的电化学电极，对经氨基乙磺酸麻醉的大鼠进行LDT刺激后丘脑NO浓度是否升高的检测。只有在LDT内插入刺激电极时，刺激后NO浓度才会短暂升高；越强的刺激产生越强的增长。结果表明，一氧化氮通过LDT神经元的兴奋从轴突末端和/或曲张中释放出来。在大鼠丘脑体外切片制备中检测了共递质的突触后作用。乙酰胆碱（ACh）可使大部分丘脑神经元去极化。当SP与乙酰胆碱同时作用时，一些神经元的去极化增强，而另一些神经元的去极化被取消，不产生静息电位变化。因此，SP作为一种共递质可以改变主递质ACh的作用，但这种改变在神经元之间是不同的。NO的作用未被清楚地证明。少

Cholinergic neurons gathering tightly in the laterodorsal tegmental nucleus (LDT) of the brainstem have nitric oxide (NO) and/or substance P (SP) as co-transmitters. The present study examined whether these co-transmitters released from axon terminals or varicosities, and what effects they gave to postsynaptic targets.In the previous study we had shown that LDT stimulation produced excitation of thalamic relay neurons which received direct projection of the cholinergic neurons. We examined in urethane-anesthetized rats, using a laser-Doppler flow meter, how the same LDT stimulation affected cerebral blood flow in the thalamus, since the co-transmitters have strong action on the blood vessels. An increase of the blood flow was observed consistently starting within several seconds after the onset of LDT stimulation and continuing about 1 minute after the stimulation. The increase was reduced by administration of scopolamine, a muscarinic antagonist, but the treatment did not block it com … More pletely.Whether NO concentration in the thalamus increased after the LDT stimulation was also examined in urethane-anesthetized rats, using electrochemical electrode sensitive specifically to NO (developed in Shionogi Research Laboratories) . The NO concentration increased transiently just after the stimulation only when the stimulating electrode was inserted in the LDT ; the stronger stimulation produced the stronger increase. The results show that NO is released from the axon terminals and/or varicosities by the excitation of LDT neurons.Postsynaptic actions of the co-transmitters were examined in in vitro slice preparations of the rat thalamus. Most thalamic neurons were depolarized by application of acetylcholine (ACh) . When SP was applied simultaneously with ACh, the depolarization was increased in some neurons, but was cancelled to produce no resting potential change in others. It is thus suggested that SP as a co-transmitter modifies the action of main transmitter ACh, but tha modification differs from neuron to neuron. Actions of NO was not demonstrated clearly. Less