Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom.
PLoS One. 2010 Jul 29;5(7):e11737. doi: 10.1371/journal.pone.0011737.
Several forms of learning, including classical conditioning of the eyeblink, depend upon the cerebellum. In examining mechanisms of eyeblink conditioning in rabbits, reversible inactivations of the control circuitry have begun to dissociate aspects of cerebellar cortical and nuclear function in memory consolidation. It was previously shown that post-training cerebellar cortical, but not nuclear, inactivations with the GABAA agonist muscimol prevented consolidation but these findings left open the question as to how final memory storage was partitioned across cortical and nuclear levels. Memory consolidation might be essentially cortical and directly disturbed by actions of the muscimol, or it might be nuclear, and sensitive to the raised excitability of the nuclear neurons following the loss of cortical inhibition. To resolve this question, we simultaneously inactivated cerebellar cortical lobule HVI and the anterior interpositus nucleus of rabbits during the post-training period, so protecting the nuclei from disinhibitory effects of cortical inactivation. Consolidation was impaired by these simultaneous inactivations. Because direct application of muscimol to the nuclei alone has no impact upon consolidation, we can conclude that post-training, consolidation processes and memory storage for eyeblink conditioning have critical cerebellar cortical components. The findings are consistent with a recent model that suggests the distribution of learning-related plasticity across cortical and nuclear levels is task-dependent. There can be transfer to nuclear or brainstem levels for control of high-frequency responses but learning with lower frequency response components, such as in eyeblink conditioning, remains mainly dependent upon cortical memory storage.
几种形式的学习，包括眨眼的经典条件反射，都依赖于小脑。在研究兔子眨眼条件反射的机制时，可逆地使控制回路失活，开始分离小脑皮质和核功能在记忆巩固中的方面。以前的研究表明，训练后用 GABAA 激动剂 muscimol 对小脑皮质而不是核进行失活可以防止巩固，但这些发现仍未解决最终记忆存储如何在皮质和核水平上进行分区的问题。记忆巩固可能本质上是皮质的，并且直接受到 muscimol 作用的干扰，也可能是核的，并且对皮质抑制丧失后核神经元兴奋性的提高敏感。为了解决这个问题，我们在训练后同时失活兔子的小脑皮质小叶 HVI 和前中间核，从而保护核免受皮质失活的去抑制作用。这些同时失活会损害巩固。由于 muscimol 直接应用于核本身对巩固没有影响，我们可以得出结论，眨眼条件反射的训练后巩固过程和记忆存储具有关键的小脑皮质成分。这些发现与最近的一个模型一致，该模型表明学习相关可塑性在皮质和核水平上的分布是任务依赖性的。对于高频反应的控制可以转移到核或脑干水平，但对于低频反应成分（如眨眼条件反射）的学习，仍然主要依赖于皮质记忆存储。
