Jabourian Maritza, Venance Laurent, Bourgoin Sylvie, Ozon Sylvie, Pérez Sylvie, Godeheu Gérard, Glowinski Jacques, Kemel Marie-Louise
INSERM U667 Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France.
Eur J Neurosci. 2005 Jun;21(12):3301-9. doi: 10.1111/j.1460-9568.2005.04154.x.
Striatal cholinergic interneurons play a crucial role in the control of movement as well as in motivational and learning aspects of behaviour. Neuropeptides regulate striatal cholinergic transmission and particularly activation of mu opioid receptor (MOR) inhibits acetylcholine (ACh) release in the dorsal striatum. In the present study we investigated whether this cholinergic transmission could be modulated by an enkephalin/MOR direct process. We show that mRNA and protein of MORs are expressed by cholinergic interneurons in the limbic/prefrontal territory but not by those in the sensorimotor territory of the dorsal striatum. These MORs are functional because potassium-evoked release of ACh from striatal synaptosomes was dose-dependently reduced by a selective MOR agonist, this effect being suppressed by a MOR antagonist. The MOR regulation of cholinergic interneurons presented a diurnal variation. (i) The percentage of cholinergic interneurons containing MORs that was 32% at the beginning of the light period (morning) increased to 80% in the afternoon. (ii) The MOR-mediated inhibition of synaptosomal ACh release was higher in the afternoon than in the morning. (iii) While preproenkephalin mRNA levels remained stable, enkephalin tissue content was the lowest (-32%) in the afternoon when the spontaneous (+35%) and the N-methyl-d-aspartate-evoked (+140%) releases of enkephalin (from microsuperfused slices) were the highest. Therefore, by acting on MORs present on cholinergic interneurons, endogenously released enkephalin reduces ACh release. This direct enkephalin/MOR regulation of cholinergic transmission that operates only in the limbic/prefrontal territory of the dorsal striatum might contribute to information processing in fronto-cortico-basal ganglia circuits.
纹状体胆碱能中间神经元在运动控制以及行为的动机和学习方面发挥着关键作用。神经肽调节纹状体胆碱能传递，特别是μ阿片受体（MOR）的激活会抑制背侧纹状体中乙酰胆碱（ACh）的释放。在本研究中，我们调查了这种胆碱能传递是否可以由脑啡肽/MOR直接过程进行调节。我们发现，MOR的mRNA和蛋白在边缘/前额叶区域的胆碱能中间神经元中表达，但在背侧纹状体的感觉运动区域的胆碱能中间神经元中不表达。这些MOR具有功能，因为选择性MOR激动剂可剂量依赖性地减少纹状体突触体中钾离子诱发的ACh释放，这种作用可被MOR拮抗剂抑制。胆碱能中间神经元的MOR调节呈现出昼夜变化。（i）含有MOR的胆碱能中间神经元的百分比在光照期开始时（早晨）为32%，下午增加到80%。（ii）MOR介导的突触体ACh释放抑制在下午高于早晨。（iii）虽然前脑啡肽原mRNA水平保持稳定，但脑啡肽组织含量在下午最低（-32%），此时脑啡肽（来自微灌注切片）的自发释放（+35%）和N-甲基-D-天冬氨酸诱发的释放（+140%）最高。因此，内源性释放的脑啡肽通过作用于胆碱能中间神经元上的MOR来减少ACh释放。这种仅在背侧纹状体的边缘/前额叶区域起作用的脑啡肽/MOR对胆碱能传递的直接调节可能有助于额-皮质-基底神经节回路中的信息处理。
