Hilber P, Caston J
UPRES PSY.CO EA 1780, Laboratoire de Neurobiologie de l'Apprentissage, Université de Rouen, Faculté des Sciences, 76821 Cedex, Mont Saint Aignan, France.
Neuroscience. 2001;102(3):615-23. doi: 10.1016/s0306-4522(00)00509-1.
Motor learning abilities on the rotorod and motor skills (muscular strength, motor coordination, static and dynamic equilibrium) were investigated in three-, nine-, 15- and 21-month-old Lurcher and control mice. Animals were subjected to motor training on the rotorod before being subjected to motor skills tests. The results showed that control mice exhibited decrease of muscular strength and specific equilibrium impairments in static conditions with age, but were still able to learn the motor task on the rotorod even in old age. These results suggest that, in control mice, efficiency of the reactive mechanisms, which are sustained by the lower transcerebellar loop (cerebello-rubro-olivo-cerebellar loop), decreased with age, while the efficiency of the proactive adjustments, which are sustained by the upper transcerebellar loop (cerebello-thalamo-cortico-ponto-cerebellar loop), did not. In spite of their motor deficits, Lurcher mutants were able to learn the motor task at three months, but exhibited severe motor learning deficits as soon as nine months. Such a deficit seems to be associated with dynamic equilibrium impairments, which also appeared at nine months in these mutants. By two months of age, degeneration of the cerebellar cortex and the olivocerebellar pathway in Lurcher mice has disrupted both lower and upper transcerebellar loops. Disruption of the lower loop could well explain precocious static equilibrium deficits. However, in spite of disruption of the upper loop, motor learning and dynamic equilibrium were preserved in young mutant mice, suggesting that either deep cerebellar nuclei and/or other motor structures involved in proactive mechanisms needed to maintain dynamic equilibrium and to learn motor tasks, such as the striatopallidal system, are sufficient. The fact that, in Lurcher mutant mice, motor learning decreased by the age of nine months suggests that the above-mentioned structures are less efficient, likely due to degeneration resulting from precocious and focused neurodegeneration of the cerebellar cortex. From this behavioral approach of motor skills and motor learning during aging in Lurcher mutant mice, we postulated the differential involvement of two transcerebellar systems in equilibrium maintenance and motor learning. Moreover, in these mutants, we showed that motor learning abilities decreased with age, suggesting that the precocious degeneration of the cerebellar Purkinje cells had long-term effects on motor structures which are not primarily affected. Thus, from these results, Lurcher mutant mice therefore appear to be a good model to study the pathological evolution of progressive neurodegeneration in the central nervous system during aging.
在3个月、9个月、15个月和21个月大的猎兔犬型突变小鼠和对照小鼠中，研究了它们在转棒试验中的运动学习能力以及运动技能（肌肉力量、运动协调性、静态和动态平衡）。在进行运动技能测试之前，先让动物在转棒上进行运动训练。结果显示，对照小鼠随着年龄增长出现肌肉力量下降和静态条件下特定的平衡受损，但即使在老年时仍能够学会转棒上的运动任务。这些结果表明，在对照小鼠中，由小脑下环路（小脑-红核-橄榄核-小脑环路）维持的反应机制效率随年龄下降，而由小脑中环路（小脑-丘脑-皮质-脑桥-小脑环路）维持的主动调节效率则没有下降。尽管存在运动缺陷，猎兔犬型突变小鼠在3个月时能够学会运动任务，但在9个月大时就表现出严重的运动学习缺陷。这种缺陷似乎与动态平衡受损有关，在这些突变小鼠9个月大时也出现了动态平衡受损。到2个月大时，猎兔犬型小鼠的小脑皮质和橄榄小脑通路退化，破坏了小脑下环路和小脑中环路。下环路的破坏很可能解释了早熟的静态平衡缺陷。然而，尽管上环路受到破坏，但年轻的突变小鼠仍保留了运动学习和动态平衡能力，这表明要么是小脑深部核团和/或其他参与主动机制以维持动态平衡和学习运动任务的运动结构，如纹状体苍白球系统，是足够的。在猎兔犬型突变小鼠中，运动学习在9个月大时下降这一事实表明，上述结构效率较低，可能是由于小脑皮质早熟且集中的神经退行性变导致的退化。从对猎兔犬型突变小鼠衰老过程中运动技能和运动学习的这种行为学研究方法中，我们推测两个小脑环路在平衡维持和运动学习中存在不同程度的参与。此外，在这些突变小鼠中，我们表明运动学习能力随年龄下降，这表明小脑浦肯野细胞的早熟退化对并非主要受影响的运动结构有长期影响。因此，从这些结果来看，猎兔犬型突变小鼠似乎是研究衰老过程中中枢神经系统进行性神经退行性变病理演变的良好模型。
