Shutoh F, Ohki M, Kitazawa H, Itohara S, Nagao S
Laboratory for Motor Learning Control, RIKEN Brain Science Institute, Hirosawa 2-1, Wako, Saitama 351-0198, Japan.
Neuroscience. 2006 May 12;139(2):767-77. doi: 10.1016/j.neuroscience.2005.12.035. Epub 2006 Feb 3.
Adaptation of ocular reflexes is a prototype of motor learning. While the cerebellum is acknowledged as the critical site for motor learning, the functional differences between the cerebellar cortex and nuclei in motor memory formation are not precisely known. Two different views are proposed: one that the memory is formed within the cerebellar flocculus, and the other that the memory is formed within vestibular nuclei. Here we developed a new paradigm of long-term adaptation of mouse horizontal optokinetic response eye movements and examined the location of its memory trace. We also tested the role of flocculus and inferior olive in long-term adaptation by chronic lesion experiments. Reversible bilateral flocculus shutdown with local application of 0.5 microl-5% lidocaine extinguished the memory trace of day-long adaptation, while it very little affected the memory trace of week-long adaptation. The responsiveness of vestibular nuclei after week-long adaptation was examined by measuring the extracellular field responses to the electrical stimulation of vestibular nerve under trichloroacetaldehyde anesthesia. The amplitudes and slopes of evoked monosynaptic field response (N1) of week-long adapted mice were enhanced around the medial vestibular nucleus compared with those of control mice. Chronic flocculus or inferior olive lesions abolished both day and week-long adaptations. These results suggest that the functional memory trace of short-term adaptation is formed initially within the cerebellar cortex, and later transferred to vestibular nuclei to be consolidated to a long-term memory. Both day and week-long adaptations were markedly depressed when neural nitric oxide was pharmacologically blocked locally and when neuronal nitric oxide synthase was ablated by gene knockout, suggesting that cerebellar long-term depression underlies both acquisition and consolidation of motor memory.
眼反射的适应性是运动学习的一个典型例子。虽然小脑被公认为是运动学习的关键部位，但小脑皮质和核在运动记忆形成中的功能差异尚不完全清楚。目前提出了两种不同的观点：一种认为记忆形成于小脑绒球内，另一种认为记忆形成于前庭核内。在这里，我们开发了一种新的小鼠水平视动反应眼动长期适应性范式，并研究了其记忆痕迹的位置。我们还通过慢性损伤实验测试了绒球和下橄榄核在长期适应性中的作用。局部应用0.5微升-5%利多卡因可逆性双侧绒球关闭消除了为期一天适应性的记忆痕迹，而对为期一周适应性的记忆痕迹影响很小。通过在三氯乙醛麻醉下测量前庭神经电刺激引起的细胞外场反应，研究了为期一周适应性后前庭核的反应性。与对照小鼠相比，为期一周适应性小鼠在内侧前庭核周围诱发的单突触场反应（N1）的幅度和斜率增强。慢性绒球或下橄榄核损伤消除了为期一天和一周的适应性。这些结果表明，短期适应性的功能性记忆痕迹最初在小脑皮质内形成，随后转移到前庭核以巩固为长期记忆。当局部药理学阻断神经型一氧化氮以及通过基因敲除消除神经元型一氧化氮合酶时，为期一天和一周的适应性均明显受到抑制，这表明小脑长期抑制是运动记忆获取和巩固的基础。
