The cerebellum, LTD, and memory: alternative views.
The cerebellum, LTD, and memory: alternative views.
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小脑、LTD 和记忆：另一种观点。
DOI：
10.1101/lm.3.6.445
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Welsh,JP
中科院分区：
文献类型：
--
作者：
Llinas,R;Lang,EJ;Welsh,JP
小脑储存运动记忆的想法在科学文献中已经变得如此普遍，以至于它经常被不加批判地作为一个事实提出。甚至今天的许多医学院教科书都指出，运动记忆位于小脑中，并且这些记忆的亚细胞基质已经在该结构中被确定。这样的前景，如果是真的，将是非常令人兴奋的;然而，应该指出的是，在小脑科学家中，即使是最基本的这些观点，也没有什么接近一致的，任何关于”小脑运动学习”的共识代表了有限数量的研究小组的观点，这些研究小组在有限数量的准备工作中进行实验。因此，我们的论文的一点是强调小脑运动学习的想法尚未得到证实，因此仍然是神经科学中最高度投机的假设之一-即使经过三十多年的积极研究。第二个问题是，所谓的运动学习的细胞基质，浦肯野细胞活动的长期抑制（LTD）的规则已经变得如此不确定和模糊，以至于有理由重新评估LTD是任何学习过程的真正机制的想法。通过对基因敲除啮齿动物的最新行为和神经生理学数据的批判性评估，这一点得到了显著的加强。然而，在细胞分子生物学和行为学的背景下，对小脑系统进行了大量的研究。因此，我们现在可以把这些发现放在现代的背景下，形成比”小脑学习“这个过时的想法更容易检验的假设。众所周知，”小脑运动学习”的概念起源于Brindley（1964）、马尔（1969）和Albus（1971）的高度推测性和完全理论性的著作。这些作品可以归功于他们的清晰度和惊人的观点小脑神经元回路。这些工作是如此大胆，以至于在学习过程中，小脑皮层的每一个抑制性中间神经元（高尔基体、篮状细胞和星状细胞）都有不同的功能，即使我们有30年的进一步研究优势，这些神经元在体内的神经生理学研究也很少。然而，Brindley-Marr-Albus模型最关键的方面是假设攀爬纤维必须扮演”教师”角色，以改变平行纤维-浦肯野细胞突触的功效。这种攀爬纤维诱导的可塑性的功能结果是改变浦肯野细胞在特定感觉环境中的输出模式，以产生新的（即学习）运动。在这些概念中，橄榄小脑系统通过其与平行纤维突触的功能相互作用，在运动中仅起间接作用。相反，苔藓纤维-平行纤维系统被视为运动指令系统
Introduction The idea that cerebellum stores motor memories has become so commonplace in the scientific literature that it is often presented uncritically as a fact. Even many of today's medical school textbooks state that motor memories are localized in the cerebellum and that the subcellular substrates of these memories have been identified in that structure. Such prospects, if true, would be very exciting; however, it should be pointed out that there is nothing close to unanimity among cerebellar scientists on even the most basic of these points and that any consensus about" cerebellar motor learning" represents the view of a limited number of research groups that perform experiments on a limited number of preparations. Thus, one point of our paper is to emphasize that the idea of cerebellar motor learning has not been demonstrated and thus remains one of the most highly speculative hypotheses in the neurosciences--even after more than three decades of active investigation. A second issue is that rules for the alleged cellular substrate of motor learning, long-term depression (LTD) of Purkinje cell activity, have become so indeterminate and ambiguous as to justify a total reevaluation of the idea that LTD is a bona fide mechanism of any learning process. That point is significantly reinforced by a critical evaluation of the most recent behavioral and neurophysiological data obtained from gene knockout rodents. Nevertheless, an impressive volume of research has been performed on the cerebellar systems in the context of cellular-molecular biology and behavior. Thus, we may now place many of those findings into a modern context to formulate hypotheses that are more easily testable than the rather timeworn idea of" cerebellar learning." As is well recognized, the concept of" cerebellar motor learning" originates from the highly speculative and completely theoretical works of Brindley (1964), Marr (1969), and Albus (1971). These works can be credited for their clarity and breathtaking views of the cerebellar neuronal circuitry. These works were so bold as to specify distinct functions for each of the inhibitory interneurons of the cerebellar cortex--Golgi, basket, and stellate cells--during the learning process, neurons about which very little in vivo neurophysiology has ever been obtained, even with our advantage of 30 years of further research. Nevertheless, the most critical aspect of the Brindley-Marr-Albus models was the assumption that the climbing fibers had to play a" teacher" role for the purpose of modifying the efficacy of the parallel fiber-Purkinje cell synapse. The functional consequence of such climbing fiber-induced plasticity was to change the pattern of Purkinje cell output in specific sensory contexts to generate novel (ie, learned) movements. In these conceptions, the olivocerebellar system played only an indirect role in movement, through its functional interaction with parallel fiber synapses. Conversely, the mossy fiber-parallel fiber system was viewed as a motor command system