Department of Neurobiology, Center for Neuroscience and Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Cereb Cortex. 2011 Jun;21(6):1362-78. doi: 10.1093/cercor/bhq217. Epub 2010 Nov 2.
Dysfunction of primary motor cortex (M1) is thought to contribute to the pathophysiology of parkinsonism. What specific aspects of M1 function are abnormal remains uncertain, however. Moreover, few models consider the possibility that distinct cortical neuron subtypes may be affected differently. Those questions were addressed by studying the resting activity of intratelencephalic-type corticostriatal neurons (CSNs) and distant-projecting lamina 5b pyramidal-tract type neurons (PTNs) in the macaque M1 before and after the induction of parkinsonism by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Contrary to previous reports, the general population of M1 neurons (i.e., PTNs, CSNs, and unidentified neurons) showed reduced baseline firing rates following MPTP, attributable largely to a marked decrease in PTN firing rates. CSN firing rates were unmodified. Although burstiness and firing patterns remained constant in M1 neurons as a whole and CSNs in particular, PTNs became more bursty post-MPTP and less likely to fire in a regular-spiking pattern. Rhythmic spiking (found in PTNs predominantly) occurred at beta frequencies (14-32 Hz) more frequently following MPTP. These results indicate that MPTP intoxication induced distinct modifications in the activity of different M1 neuronal subtypes. The particular susceptibility of PTNs suggests that PTN dysfunction may be an important contributor to the pathophysiology of parkinsonian motor signs.
原发性运动皮层(M1)功能障碍被认为是帕金森病病理生理学的原因。然而,M1 功能的哪些具体方面异常仍不确定。此外,很少有模型考虑到不同皮质神经元亚型可能受到不同影响的可能性。通过在恒河猴 M1 中施用 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导帕金森病之前和之后研究内脑型皮质纹状体神经元(CSN)和远距离投射的第 5b 层金字塔形束型神经元(PTN)的静息活动,解决了这些问题。与之前的报道相反,MPTP 后,M1 神经元(即 PTN、CSN 和未鉴定神经元)的总体基线放电率降低,主要归因于 PTN 放电率的显著降低。CSN 的放电率没有改变。尽管 M1 神经元整体和 CSN 特别是爆发性和放电模式保持不变,但 PTN 在 MPTP 后变得更具爆发性,不太可能以规则的尖峰模式放电。节律性尖峰(主要存在于 PTN 中)在 MPTP 后更频繁地发生在β频带(14-32 Hz)。这些结果表明,MPTP 中毒诱导了不同 M1 神经元亚型活性的不同改变。PTN 的特殊易感性表明,PTN 功能障碍可能是帕金森运动体征病理生理学的重要原因。