Functional roles of co-transmitters in brainsten cholinergic neurons

紧密聚集在脑干被盖外侧核(LDT)的胆碱能神经元含有一氧化氮(NO)和/或P物质(SP)作为共同递质。本研究检测了这些共递质是否从轴突终末或突起释放，以及它们对突触后靶点的影响。在先前的研究中，我们已经证明，刺激LDT产生了丘脑中继神经元的兴奋，该神经元接受胆碱能神经元的直接投射。我们在乌拉坦麻醉的大鼠身上，使用激光多普勒血流计，研究了同样的LDT刺激如何影响丘脑的脑血流，因为协同递质对血管有很强的作用。在LDT刺激开始后的几秒钟内，观察到持续的血流量增加，并在刺激后持续约1分钟。这种增加可以通过给予M受体拮抗剂东莨菪碱来减少，但这种治疗并不能阻断它的…在乌拉坦麻醉的大鼠中，使用对NO特别敏感的电化学电极(由Shionogi研究实验室开发)，也检测了刺激LDT后丘脑中的NO浓度是否增加。只有当刺激电极插入LDT时，刺激后NO浓度才有一过性升高，刺激强度越大，NO浓度升高幅度越大。结果表明，在LDT神经元的兴奋下，轴突终末和/或静脉曲张释放出NO。在体外制作的大鼠丘脑脑片上观察了共同递质的突触后作用。应用乙酰胆碱(ACh)可使大部分丘脑神经元去极化。当SP与ACh同时应用时，部分神经元的去极化作用增强，而另一些神经元的去极化作用被取消而不引起静息电位的改变。因此，提示SP作为一种共递质可以改变主递质ACh的作用，但不同神经元的作用不同。NO的作用没有清楚地显示出来。较少

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