Shimo Yasushi, Wichmann Thomas
Department of Neurology, School of Medicine, Emory University, Atlanta, GA, USA.
Eur J Neurosci. 2009 Jan;29(1):104-13. doi: 10.1111/j.1460-9568.2008.06565.x. Epub 2008 Dec 12.
The primate subthalamic nucleus (STN) is commonly seen as a relay nucleus between the external and internal pallidal segments, and as an input station for cortical and thalamic information into the basal ganglia. In rodents, STN activity is also known to influence neuronal activity in the dopaminergic substantia nigra pars compacta (SNc) through inhibitory and excitatory mono- and polysynaptic pathways. Although the anatomical connections between STN and SNc are not entirely the same in primates as in rodents, the electrophysiologic and microdialysis experiments presented here show directly that this functional interaction can also be demonstrated in primates. In three Rhesus monkeys, extracellular recordings from SNc during microinjections into the STN revealed that transient pharmacologic activation of the STN by the acetylcholine receptor agonist carbachol substantially increased burst firing of single nigral neurons. Transient inactivation of the STN with microinjections of the GABA-A receptor agonist muscimol had the opposite effect. While the firing rates of individual SNc neurons changed in response to the activation or inactivation of the STN, these changes were not consistent across the entire population of SNc cells. Permanent lesions of the STN, produced in two animals with the fiber-sparing neurotoxin ibotenic acid, reduced burst firing and firing rates of SNc neurons, and substantially decreased dopamine levels in the primary recipient area of SNc projections, the striatum, as measured with microdialysis. These results suggest that activity in the primate SNc is prominently influenced by neuronal discharge in the STN, which may thus alter dopamine release in the striatum.
灵长类动物的丘脑底核（STN）通常被视为苍白球外部和内部节段之间的中继核，以及皮质和丘脑信息传入基底神经节的输入站。在啮齿动物中，已知STN活动通过抑制性和兴奋性单突触及多突触途径影响多巴胺能黑质致密部（SNc）的神经元活动。尽管灵长类动物中STN与SNc之间的解剖学联系与啮齿动物并不完全相同，但本文所呈现的电生理和微透析实验直接表明，这种功能相互作用在灵长类动物中也能得到证实。在三只恒河猴中，向STN进行微量注射期间对SNc进行细胞外记录发现，乙酰胆碱受体激动剂卡巴胆碱对STN的短暂药理学激活显著增加了单个黑质神经元的爆发性放电。注射GABA - A受体激动剂蝇蕈醇使STN短暂失活则产生相反的效果。虽然单个SNc神经元的放电频率会因STN的激活或失活而改变，但这些变化在整个SNc细胞群体中并不一致。用纤维保留神经毒素鹅膏蕈氨酸对两只动物造成STN永久性损伤，降低了SNc神经元的爆发性放电和放电频率，并用微透析法测量发现，SNc投射的主要接受区域纹状体中的多巴胺水平大幅下降。这些结果表明，灵长类动物SNc中的活动受到STN神经元放电的显著影响，进而可能改变纹状体中的多巴胺释放。
