Nigrostriatal lesion and dopamine agonists affect firing patterns of rodent entopeduncular nucleus neurons.
Nigrostriatal lesion and dopamine agonists affect firing patterns of rodent entopeduncular nucleus neurons.
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DOI：
10.1152/jn.00844.2001
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发表时间：
2002-07
影响因子：
2.5
通讯作者：
D. N. Ruskin;D. A. Bergstrom;J. R. Walters
中科院分区：
文献类型：
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作者：
D. N. Ruskin;D. A. Bergstrom;J. R. Walters
改变活动的脚内核，在灵长类动物的苍白球内段的啮齿动物同源物，被认为是介导的行为后果的中脑多巴胺耗竭的啮齿动物。然而，很少有研究探讨多巴胺能调制的尖峰活动在这个核。本研究描述了黑质纹状体多巴胺能损伤后脚内核神经元活动的变化，以及选择性D（1）（SKF 38393）和D（2）（喹吡罗）激动剂全身治疗对损伤大鼠的影响。在清醒的固定大鼠中进行细胞外单单位记录，无论是在神经系统完整的动物（n = 42），或在接受了单侧6-羟基多巴胺输注到内侧前脑束数周前（n = 35）的动物。黑质纹状体损伤改变了脚内核神经元的基线活动在几个方面。峰间期分布有显着减少的模式和显着增加的变异系数，偏度和峰度，但峰间期平均值（发射率的倒数）不受影响。此外，自相关图的频谱分析表明，损伤显着减少了规则尖峰神经元的发生率，并增加了4-18 Hz振荡的神经元的发生率。多巴胺激动剂治疗逆转了一些损伤诱导的效应：喹吡罗逆转了棘波间期分布模式和变异系数的变化，而喹吡罗和SKF 38393联合使用则阻断了4-18 Hz振荡的出现。然而，没有激动剂治疗正常化的脚内活动的所有方面。此外，D（1）或D（1）/D（2）受体联合激活对放电率的抑制表明，多巴胺激动剂以与多巴胺神经元损伤后在黑质网状部和苍白球内段中发现的相似的方式影响脚内核活动的总体水平。这些数据表明，黑质纹状体束的病变导致啮齿动物脚内核的放电模式的几个方面的修改，因此扩大在啮齿动物黑质网状部和人类和非人灵长类动物的苍白球内段类似的研究结果。结果支持这样的观点，即中脑多巴胺神经元丧失后基底神经节的功能障碍与异常活动模式的关系比与基底神经节输出核团放电率的净变化的关系更为一致，而这些结构中放电率的总体下降可能在多巴胺受体激动剂治疗的不良运动反应中发挥更重要的作用。
Altered activity of the entopeduncular nucleus, the rodent homologue of the globus pallidus internal segment in primates, is thought to mediate behavioral consequences of midbrain dopamine depletion in rodents. Few studies, however, have examined dopaminergic modulation of spiking activity in this nucleus. This study characterizes changes in entopeduncular neuronal activity after nigrostriatal dopaminergic lesion and the effects of systemic treatment with selective D(1) (SKF 38393) and D(2) (quinpirole) agonists in lesioned rats. Extracellular single-unit recordings were performed in awake immobilized rats, either in neurologically intact animals (n = 42) or in animals that had received unilateral 6-hydroxydopamine infusion into the medial forebrain bundle several weeks previously (n = 35). Nigrostriatal lesion altered baseline activity of entopeduncular neurons in several ways. Interspike interval distributions had significantly decreased modes and significantly increased coefficient of variation, skewness and kurtosis; yet interspike interval mean (the inverse of firing rate) was not affected. Also, spectral analysis of autocorrelograms indicated that lesion significantly reduced the incidence of regular-spiking neurons and increased the incidence of neurons with 4-18 Hz oscillations. Dopamine agonist treatment reversed some lesion-induced effects: quinpirole reversed changes in interspike interval distribution mode and coefficient of variation, while combined quinpirole and SKF 38393 blocked the appearance of 4-18 Hz oscillations. However, no agonist treatment normalized all aspects of entopeduncular activity. Additionally, inhibition of firing rates by D(1) or combined D(1)/D(2) receptor activation indicated that dopamine agonists affected the overall level of entopeduncular activity in a manner similar to that found in the substantia nigra pars reticulata and globus pallidus internal segment after dopamine neuron lesion. These data demonstrate that lesion of the nigrostriatal tract leads to modifications of several aspects of firing pattern in the rodent entopeduncular nucleus and so expand on similar findings in the rodent substantia nigra pars reticulata and in the globus pallidus internal segment in humans and nonhuman primates. The results support the view that dysfunction in the basal ganglia after midbrain dopamine neuron loss relates more consistently to abnormal activity patterns than to net changes in firing rate in the basal ganglia output nuclei, while overall decreases in firing rate in these structures may play a more important role in adverse motor reactions to dopamine agonist treatments.