Extrastriatal D2-like receptors modulate basal ganglia pathways in normal and parkinsonian monkeys
Extrastriatal D2-like receptors modulate basal ganglia pathways in normal and parkinsonian monkeys
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DOI：
10.1152/jn.00348.2011
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发表时间：
2012-03-01
影响因子：
2.5
通讯作者：
Wichmann, Thomas
中科院分区：
文献类型：
--
作者：
Hadipour-Niktarash, Arash;Rommelfanger, Karen S.;Wichmann, Thomas
吴伟杰，王晓刚.纹状体外D2样受体调节正常和帕金森病猴的基底神经节通路J Neurophysiol 107：1500-1512，2012.首次发表于2011年11月30日; doi：10.1152/jn.00348.2011.-根据基底神经节-丘脑皮质网络连接的传统模型，多巴胺通过对纹状体神经元的作用产生D2样受体（D2 LR）介导的效应，引起“间接”途径，其次影响苍白球内外段（分别为GPi和GPe）和黑质网状部（SNr）的活性。然而，越来越多的证据表明，从啮齿动物的文献表明，D2 LR激活也直接影响这些核中的突触传递。为了进一步研究这个问题在灵长类动物中，我们结合在体内电生理记录和局部脑内微量注射的药物与电子显微镜免疫细胞化学研究D2 LR介导的调制正常和MPTP治疗（帕金森病）猴的GPe，GPi和SNr的神经元活动。用喹吡罗激活D2 LR增加了大多数GPe神经元的放电，这可能是由于纹状体苍白球GABA能输入的减少。与此相反，局部应用quinpirole减少射击GPi和SNr，可能是通过D2 LR介导的影响，对amatergic输入。注射D2 LR拮抗剂舒必利导致GPe和GPi中与quinpirole相反的效果。D2受体的免疫反应是最普遍的，在假定的纹状体样GABA能终端和无髓轴突在GPe，GPi，和SNr，但一个显着比例的免疫反应终末也显示出超微结构特征的GABA能终端。突触后标记是最小的所有核。D2 LR介导的作用和D2受体免疫反应性的分布模式维持在帕金森状态。因此，除了它们对间接通路纹状体神经元的优先作用外，GPi和SNr中的纹状体外D2 LR激活还影响正常和帕金森病条件下灵长类动物基底神经节中的直接通路元件。
Hadipour-Niktarash A, Rommelfanger KS, Masilamoni GJ, Smith Y, Wichmann T. Extrastriatal D2-like receptors modulate basal ganglia pathways in normal and parkinsonian monkeys. J Neurophysiol 107: 1500-1512, 2012. First published November 30, 2011; doi:10.1152/jn.00348.2011.-According to traditional models of the basal ganglia-thalamocortical network of connections, dopamine exerts D2-like receptor (D2LR)-mediated effects through actions on striatal neurons that give rise to the "indirect" pathway, secondarily affecting the activity in the internal and external pallidal segments (GPi and GPe, respectively) and the substantia nigra pars reticulata (SNr). However, accumulating evidence from the rodent literature suggests that D2LR activation also directly influences synaptic transmission in these nuclei. To further examine this issue in primates, we combined in vivo electrophysiological recordings and local intracerebral microinjections of drugs with electron microscopic immunocytochemistry to study D2LR-mediated modulation of neuronal activities in GPe, GPi, and SNr of normal and MPTP-treated (parkinsonian) monkeys. D2LR activation with quinpirole increased firing in most GPe neurons, likely due to a reduction of striatopallidal GABAergic inputs. In contrast, local application of quinpirole reduced firing in GPi and SNr, possibly through D2LR-mediated effects on glutamatergic inputs. Injections of the D2LR antagonist sulpiride resulted in effects opposite to those of quinpirole in GPe and GPi. D2 receptor immunoreactivity was most prevalent in putative striatal-like GABAergic terminals and unmyelinated axons in GPe, GPi, and SNr, but a significant proportion of immunoreactive boutons also displayed ultrastructural features of glutamatergic terminals. Postsynaptic labeling was minimal in all nuclei. The D2LR-mediated effects and pattern of distribution of D2 receptor immunoreactivity were maintained in the parkinsonian state. Thus, in addition to their preferential effects on indirect pathway striatal neurons, extrastriatal D2LR activation in GPi and SNr also influences direct pathway elements in the primate basal ganglia under normal and parkinsonian conditions.