Université Bordeaux Segalen, Centre National de la Recherche Scientifique (CNRS UMR 5293), Neurodegenerative Diseases Institute, 146 rue Léo-Saignat, 33076 Bordeaux Cedex, France.
Neuroscience. 2012 Jan 27;202:424-33. doi: 10.1016/j.neuroscience.2011.11.024. Epub 2011 Nov 25.
Parkinson's disease (PD) is characterized by a degeneration of dopaminergic neurons and also by a degradation of noradrenergic neurons from the locus coeruleus and serotonergic neurons from the dorsal raphe. However, the effect of these depletions on the neuronal activity of basal ganglia nuclei is still unknown. By using extracellular single-unit recordings, we have addressed this question by testing the effects of selective depletions of noradrenaline (NA) (with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4)) and serotonin (5-HT) (with 4-chloro-l-phenylalanine (pCPA)) on the neuronal activity of globus pallidus (GP) and substantia nigra pars reticulata (SNr) neurons in the 6-hydroxydopamine (6-OHDA) rat model of PD and sham-lesioned rats. We showed that 6-OHDA-induced dopamine (DA) depletion resulted in an increased number of GP and SNr neurons discharging in a bursty and irregular manner, confirming previous studies. These pattern changes were region-dependently influenced by additional monoamine depletion. Although the number of irregular and bursty neurons in 6-OHDA rats tended to decrease in the GP after NA depletion, it did not change after pCPA treatment in both GP and SNr. Furthermore, a significant interaction between DA and 5-HT depletions was observed on the firing rate of SNr neurons. By themselves, NA depletion did not change GP or SNr neuronal activity, whereas 5-HT depletion decreased the firing rate and increased the proportion of bursty and irregular neurons in both brain regions, suggesting that 5-HT, but not NA, plays a major role in the modulation of both the firing rate and patterns of GP and SNr neurons. Finally, our data suggest that, in addition to the primary role of DA in the control of basal ganglia activity, NA and 5-HT depletion also contribute to the dysregulation of the basal ganglia in PD by changes to neuronal firing patterns.
帕金森病（PD）的特征是多巴胺能神经元退化，以及蓝斑核的去甲肾上腺素能神经元和中缝背核的 5-羟色胺能神经元退化。然而，这些耗竭对基底神经节核团神经元活动的影响尚不清楚。通过使用细胞外单细胞记录，我们通过测试选择性耗竭去甲肾上腺素（NA）（用 N-（2-氯乙基）-N-乙基-2-溴苯甲胺盐酸盐（DSP-4））和 5-羟色胺（5-HT）（用 4-氯-L-苯丙氨酸（pCPA））对 6-羟多巴胺（6-OHDA）诱导的 PD 大鼠模型和假损伤大鼠苍白球（GP）和黑质网状部（SNr）神经元的神经元活动的影响来解决这个问题。我们表明，6-OHDA 诱导的多巴胺（DA）耗竭导致 GP 和 SNr 神经元以爆发性和不规则的方式放电的神经元数量增加，这证实了以前的研究。这些模式变化与额外的单胺耗竭在区域上相关。尽管在 GP 中，NA 耗竭后 6-OHDA 大鼠中不规则和爆发性神经元的数量趋于减少，但在 GP 和 SNr 中，pCPA 处理后并未改变。此外，还观察到 SNr 神经元放电率上存在 DA 和 5-HT 耗竭的显著相互作用。单独来看，NA 耗竭不会改变 GP 或 SNr 神经元的活性，而 5-HT 耗竭会降低两个脑区的放电率并增加爆发性和不规则神经元的比例，这表明 5-HT 而非 NA 在调节 GP 和 SNr 神经元的放电率和模式中起着主要作用。最后，我们的数据表明，除了 DA 在基底神经节活动控制中的主要作用外，NA 和 5-HT 耗竭还通过改变神经元放电模式导致 PD 中基底神经节的失调。
