Lobb C J, Jaeger D
Department of Biology, Emory University, Atlanta, GA 30322, USA.
Department of Biology, Emory University, Atlanta, GA 30322, USA.
Neurobiol Dis. 2015 Mar;75:177-85. doi: 10.1016/j.nbd.2014.12.026. Epub 2015 Jan 6.
Electrophysiological changes in basal ganglia neurons are hypothesized to underlie motor dysfunction in Parkinson's disease (PD). Previous results in head-restrained MPTP-treated non-human primates have suggested that increased bursting within the basal ganglia and related thalamic and cortical areas may be a hallmark of pathophysiological activity. In this study, we investigated whether there is increased bursting in substantia nigra pars reticulata (SNpr) output neurons in anesthetized and awake, head-restrained unilaterally lesioned 6-OHDA mice when compared to control mice. Confirming previous studies, we show that there are significant changes in the firing rate and pattern in SNpr neuron activity under urethane anesthesia. The regular firing pattern of control urethane-anesthetized SNpr neurons was not present in the 6-OHDA-lesioned group, as the latter neurons instead became phase locked with cortical slow wave activity (SWA). Next, we examined whether such robust electrophysiological changes between groups carried over to the awake state. SNpr neurons from both groups fired at much higher frequencies in the awake state than in the anesthetized state and surprisingly showed only modest changes between awake control and 6-OHDA groups. While there were no differences in firing rate between groups in the awake state, an increase in the coefficient of variation (CV) was observed in the 6-OHDA group. Contrary to the bursting hypothesis, this increased CV was not due to changes in bursting but was instead due to a mild increase in pausing. Together, these results suggest that differences in SNpr activity between control and 6-OHDA lesioned mice may be strongly influenced by changes in network activity during different arousal and behavioral states.
基底神经节神经元的电生理变化被认为是帕金森病（PD）运动功能障碍的基础。先前对头部固定的MPTP处理的非人类灵长类动物的研究结果表明，基底神经节以及相关丘脑和皮质区域内爆发性活动增加可能是病理生理活动的一个标志。在本研究中，我们调查了与对照小鼠相比，在麻醉和清醒、头部固定的单侧6-OHDA损伤小鼠中，黑质网状部（SNpr）输出神经元的爆发性活动是否增加。与先前的研究一致，我们发现在乌拉坦麻醉下，SNpr神经元活动的放电频率和模式有显著变化。在6-OHDA损伤组中，对照乌拉坦麻醉的SNpr神经元的规则放电模式不存在，因为后者的神经元反而与皮质慢波活动（SWA）出现锁相。接下来，我们研究了两组之间如此明显的电生理变化是否会延续到清醒状态。两组的SNpr神经元在清醒状态下的放电频率都比麻醉状态下高得多，令人惊讶的是，清醒对照和6-OHDA组之间仅表现出适度的变化。虽然在清醒状态下两组之间的放电频率没有差异，但在6-OHDA组中观察到变异系数（CV）增加。与爆发性假说相反，这种CV增加不是由于爆发性活动的变化，而是由于停顿的轻度增加。总之，这些结果表明，对照和6-OHDA损伤小鼠之间SNpr活动的差异可能受到不同觉醒和行为状态下网络活动变化的强烈影响。
