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首页> 外文期刊>The European Journal of Neuroscience >Modulatory action of acetylcholine on striatal neurons: microiontophoretic study in awake, unrestrained rats.
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Modulatory action of acetylcholine on striatal neurons: microiontophoretic study in awake, unrestrained rats.

机译：乙酰胆碱对纹状体神经元的调节作用：清醒，不受约束的大鼠的微离子电渗疗法研究。

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Cholinergic interneurons innervate virtually all medium spiny striatal cells, but the relevance of this input in regulating the activity and afferent responsiveness of these cells remains unclear. Studies in anaesthetized animals and slice preparations have shown that iontophoretic acetylcholine (ACh) either weakly excites or inhibits striatal neurons. These differential responses may reflect cholinergic receptor heterogeneity but may be also related to the different activity states of recorded units and different afferent inputs specific in each preparation. Single-unit recording was combined with iontophoresis in awake, unrestrained rats to examine the effects of ACh and selective muscarinic (oxotremorine M or Oxo-M) and nicotinic agonists (nicotine or NIC) on dorsal and ventral striatal neurons. These effects were tested on naturally silent, spontaneously active and glutamate-stimulated units. We found that iontophoretic ACh primarily inhibited spontaneously active and glutamate-stimulated units; the direction of the ACh response, however, was dependent on the firing rate. The effects of ACh were generally mimicked by Oxo-M and, surprisingly, by NIC, which is known to excite units in most central structures, including striatal neurons in anaesthetized preparation. Given that NIC receptors are absent on striatal cells but located primarily on dopamine terminals, we assessed the effects of NIC after complete blockade of dopamine receptors induced by systemic administration of a mixture of D1 and D2 antagonists. During dopamine receptor blockade the number of NIC-induced inhibitions dramatically decreased and NIC had mainly excitatory effects on striatal neurons. Thus, our data suggest that under physiologically relevant conditions ACh acts as a state-dependent neuromodulator, and its action involves not only postsynaptic but also presynaptic cholinoreceptors located on dopamine- and glutamate-containing terminals.
机译：胆碱能中间神经实际上支配着所有的中性多刺纹状体细胞，但是尚不清楚这种输入与调节这些细胞的活性和传入反应的相关性。对麻醉动物和切片制剂的研究表明，离子电渗乙酰基胆碱（ACh）既不易激发也可以抑制纹状体神经元。这些差异反应可能反映了胆碱能受体的异质性，但也可能与记录单位的不同活性状态和每种制剂中特定的不同传入输入有关。在清醒，不受约束的大鼠中，将单单位记录与离子电渗疗法相结合，以检查ACh和选择性毒蕈碱（氧代莫来因M或Oxo-M）和烟碱激动剂（尼古丁或NIC）对背侧和腹侧纹状体神经元的影响。在自然沉默，自发活动和谷氨酸刺激的单位上测试了这些效果。我们发现离子电渗乙酰胆碱主要抑制自发活性和谷氨酸刺激的单位。但是，ACh反应的方向取决于发射速率。 ACh的作用通常被Oxo-M和令人惊讶的NIC所模仿，而NIC被认为可以激发大多数中央结构的单位，包括麻醉制剂中的纹状体神经元。鉴于纹状体细胞上不存在NIC受体，但主要位于多巴胺末端，我们在完全阻断D1和D2拮抗剂混合物的全身给药引起的多巴胺受体完全阻断后，评估了NIC的作用。在多巴胺受体阻滞期间，NIC引起的抑制作用的数量急剧减少，并且NIC主要对纹状体神经元具有兴奋作用。因此，我们的数据表明，在生理相关条件下，ACh充当状态依赖性神经调节剂，其作用不仅涉及位于多巴胺和谷氨酸末端的突触后胆碱受体，而且还涉及突触前胆碱受体。

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