Motor skills and motor learning in lurcher mutant mice during aging

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 mu scular strength and specific equilibrium impairments in static conditions w ith 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 re active mechanisms, which are sustained by the lower transcerebellar loop (c erebello- rubro-olivo -cerebellar loop), decreased with age, while the effi ciency of the proactive adjustments, which are sustained by the upper trans cerebellar loop (cerebello-thalamo-cortico-ponto-cerebellar loop), did not. In spite of their motor deficits, Lurcher mutants were able to learn the m otor task at three months, but exhibited severe motor learning deficits as soon as nine months. Such a deficit seems to be associated with dynamic equ ilibrium impairments, which also appeared at nine months in these mutants. By two months of age, degeneration of the cerebellar cortex and the olivoce rebellar pathway in Lurcher mice has disrupted both lower and upper transce rebellar loops. Disruption of the lower loop could well explain precocious static equilibrium deficits. However, in spite of disruption of the upper l oop, motor learning and dynamic equilibrium were preserved in young mutant mice, suggesting that either deep cerebellar nuclei and/or other motor stru ctures involved in proactive mechanisms needed to maintain dynamic equilibr ium and to learn motor tasks, such as the striatopallidal system, are suffi cient. The fact that, in Lurcher mutant mice, motor learning decreased by t he age of nine months suggests that the above-mentioned structures are less efficient, likely due to degeneration resulting from precocious and focuse d neurodegeneration of the cerebellar cortex. From this behavioral approach of motor skills and motor learning during agi ng in Lurcher mutant mice, we postulated the differential involvement of tw o transcerebellar systems in equilibrium maintenance and motor learning. Mo reover, in these mutants, we showed that motor learning abilities decreased with age, suggesting that the precocious degeneration of the cerebellar Pu rkinje cells had long-term effects on motor structures which are not primar ily affected. Thus, from these results, Lurcher mutant mice therefore appea r to be a good model to study the pathological evolution of progressive neu rodegenera tion in the central nervous system during aging. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.