Interactive reportMechanisms of motor learning in the cerebellum1
Introduction
Motor learning is a function of the brain for acquiring new repertoires of movements and skills to perform them through practice, and it involves many areas of the brain. The prefrontal cerebral cortex is responsible for planning movements, and its premotor area for programming movements. The motor cortex, which forms commands sent to the lower motor centers in the brain stem and spinal cord, undergoes reorganization in motor learning [3]. Sensory and temporoparietal association areas may also be involved in learning to improve the perceptual capability required for movements. At subcortical levels, the basal ganglia and cerebellum are the two major structures involved in motor learning. Even the brain stem and spinal cord may contribute to motor learning to a certain extent based on their experience-dependent plasticity.
Results of classic lesion studies, as compiled by Dow and Moruzzi [14], suggest that the contribution of the cerebellum to motor learning is to enable us to learn to perform accurate and smooth movements, even at high speeds and without visual feedback. A central question addressed has been how this function originates from the elaborate neuronal circuit structure of the cerebellum as already described in detail early in the 20th century by Cajal [6]. Before 1960, while researchers with an experimental focus were engaged in anatomical [37] and lesion studies of the cerebellum [14], theorists formulated general neuronal network models as represented by Hebb’s [25] neuron assembly and Rosenblatt’s [72] Simple Perceptron. The two groups began to work closely with each other when an elaborate neuronal circuit in the cerebellum was revealed, as summarised in Eccles et al. [16] (Fig. 1). This experimental–theoretical interaction resulted in proposals of epochal network theories of the cerebellum by Marr [57], Albus [2] and others around 1970, which motivated subsequent experimental efforts to verify the theories. Much effort has since been devoted both theoretically and experimentally to produce a significant progress in our understanding of neural mechanisms of the cerebellum. In this article, we focus on the hypothesis that error-driven LTD-based reorganization of the neuronal circuit in a microcomplex, functional module of the cerebellum is a major mechanism of motor learning.
Section snippets
Circuit and module structures of the cerebellum
In the cerebellar cortex, Purkinje cells (PCs) in the cerebellar cortex receive input from axons of granule cells (GAs) that relay mossy fibers (MFs) arising from diverse precerebellar nuclei (Fig. 1). GAs ascend from the granular layer to the molecular layer and bifurcate to parallel fibers (PFs), which extend by 2–3 mm on each side. Each PC receives as many as 60 000 to 175 000 PFs on their dendritic spines [65], [69]. The ascending segments also contribute about 20% of the total GA input,
Long-term depression (LTD)
As any computer requires memory elements, the neuronal circuit in the cerebellum was suggested to have a type of synaptic plasticity as memory element [2], [57]. In the 1980s, heterosynaptic LTD (referred to as LTD hereafter) was discovered and established as a unique, characteristic synaptic plasticity in the cerebellum [32], [35], [36], [17]. LTD occurs when impulses of a set of GAs and one CF reach the same PC synchronously and repeatedly; synaptic transmission from the GAs to the PC is then
Signal transduction for LTD
Various reduced forms of LTD have been generated by replacing stimulation by either GAs or CFs, or both, with chemical stimulation or application of electrical currents to PCs. In cerebellar slices, the CF stimulation can be replaced by the application of depolarizing pulses, which bring about the entry of Ca2+ ions into PCs through voltage-gated channels. In cultured PCs devoid of both GAs and CFs, a reduced form of LTD is induced by a combination of glutamate (or quisqualate) pulses and
Error representation by CFs
Since the 1970s, various experimental paradigms for testing cerebellar function such as vestibulo-ocular reflex adaptation [15], [19], [30], hand/arm movement [20], eyeblink conditioning [58] and locomotion [27], [85] have been developed, and the contents of signals generated by cerebellar neurons in these paradigms were analysed.
Arrival of CF signals at a PC is indicated by the generation of complex spikes from the PC [80]. In simple situations such as reflexes, CFs convey sensory signals such
Involvement of LTD in motor learning
Roles of LTD in motor learning have been tested by two methods of observation: (1) Whether PC activities are modified in motor learning in a manner consistent with the occurrence of LTD [20], [30], [78], and (2) whether blockade of LTD impairs motor learning. The second method is effective in demonstrating the involvement of LTD in motor learning, when other types of synaptic plasticity exist in the cerebellar circuit and other roles of LTD such as prevention of overexcitation of PCs [12] or Ca
Towards 2010
Toward the final goal of understanding learning mechanisms of the cerebellum, the following two questions are to be addressed.
First, how is LTD eventually converted to permanent memory? The observation time for LTD is usually limited to 0.5 to 1 h, and occasionally for 2 to 3 h. LTD induced in mEPSCs in cultured PCs by conjunctive application of 50 mM K+ and 100 μM glutamate was observed to last for 36 h and return to the original level after 48 h [62]. This observation, however, would not
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Published on the World Wide Web on 24 November 2000.