Departmental Bulletin Paper 運動の順序およびスキル学習のマウス・モデルとしての3レバー・オペラント課題の利用可能性
Availability of three-lever operant task as mouse model for studying motor sequence and skill learning

米田, 貢  ,  田端, 佑樹  ,  越後, 亮介  ,  菊池, ゆひ  ,  少作, 隆子

39 ( 2 )  , pp.113 - 123 , 2016-01-27 , 金沢大学つるま保健学会 = Tsuruma Health Science Society, Kanazawa University
Human behavior in daily life is based on various brain functions, including cognitive and motor functions. A better understanding of neural mechanisms underlying motor learning is an important prerequisite for the development of treatments and has important clinical implications. Previous studies developed a sequence and skill learning task, called “three-lever operant task,” where rats were trained to press three levers in correct order within a given time, and demonstrated that this task is dependent on the basal ganglia. As genetically altered mice have been shown to be useful for studying the molecular mechanisms underlying brain functions, we applied the three-lever operant task to mice and examined whether this task can be used as a mouse model for studying motor sequence and skill learning.  Experiments were carried out with five C57BL/6NCr male mice at the age of 8 weeks. One training session lasting 60 minutes was given once a day, five times a week. Mice were trained to press any one of active levers for food reinforcement (R) (one-lever task), three levers in a given sequence within a given time (T) (three-lever task), and three levers in the opposite sequence (reverse three-lever task).  Analysis of the performance in the one-lever task, which was used as a shaping procedure for the three-lever task, demonstrated that mice change their behavior after inactivation of the most frequently pressed lever, and that this behavioral change can be evaluated quantitatively from the inactive lever press ratio. In the three-lever task, the number of sessions required to learn the order without time restriction ranged from 4 to 16 sessions (1 ‒ 3 weeks), which was comparable to that in rats (1 ‒ 4 weeks). In the three-lever task with time restriction, the mice showed good performance (R > 100) even at T = 0.6 s. In the reverse three-lever task, mice relearned the order of lever press within three sessions, indicating that this task can be used to study reversal learning. These results indicate that the three-lever operant task is useful for studying several different aspects of motor learning, including sequence learning, skill learning, adaptation, and reversal learning. We expect that the application of this task to various types of genetically altered mice will yield substantial progress in understanding the neural mechanisms of motor learning.

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