Inagaki Keiichiro, Hirata Yutaka
Department of Robotic Science and Technology, College of Engineering, Chubu University, 1200 Matsumoto, Kasugai, Aichi, 487-8501, Japan.
Cerebellum. 2017 Aug;16(4):827-839. doi: 10.1007/s12311-017-0857-6.
The vestibulo-ocular reflex (VOR) can be viewed as an adaptive control system that maintains compensatory eye movements during head motion. As the cerebellar flocculus is intimately involved in this adaptive motor control of the VOR, the VOR has been a popular model system for investigating cerebellar motor learning. Long-term depression (LTD) and long-term potentiation (LTP) at the parallel fiber-Purkinje cell synapses are considered to play major roles in cerebellar motor learning. A recent study using mutant mice demonstrated cerebellar motor learning with hampered LTD; the study concluded that the parallel fiber-Purkinje cell LTD is not essential. More recently, multiple forms of plasticity have been found in the cerebellum, and they are believed to contribute to cerebellar motor learning. However, it is still unclear how synaptic plasticity modifies the signal processing that underlies motor learning in the flocculus. A computational simulation suggested that the plasticity present in mossy fiber-granule cell synapses improves VOR-related sensory-motor information transferred into granule cells, whereas the plasticity in the molecular layer stores this information as a memory under guidance from climbing fiber teaching signals. Thus, motor learning and memory are thought to be induced mainly by LTD and LTP at parallel fiber-Purkinje cell synapses and by rebound potentiation at molecular interneuron-Purkinje cell synapses among the multiple forms of plasticity in the cerebellum. In this study, we focused on the LTD and LTP at parallel fiber-Purkinje cell synapses. Based on our simulation, we propose that acute VOR motor learning accomplishes by simultaneous enhancement of eye movement signals via LTP and suppression of vestibular signals via LTD to increase VOR gain (gain-up learning). To decrease VOR gain (gain-down learning), these two signals are modified in the opposite directions; namely, LTD suppresses eye movement signals, whereas LTP enhances vestibular signals.
前庭眼反射（VOR）可被视为一种自适应控制系统，它在头部运动期间维持代偿性眼球运动。由于小脑绒球密切参与VOR的这种自适应运动控制，VOR一直是研究小脑运动学习的常用模型系统。平行纤维-浦肯野细胞突触处的长时程抑制（LTD）和长时程增强（LTP）被认为在小脑运动学习中起主要作用。最近一项使用突变小鼠的研究表明，小脑运动学习存在LTD受阻的情况；该研究得出结论，平行纤维-浦肯野细胞LTD并非必不可少。最近，在小脑中发现了多种形式的可塑性，并且它们被认为有助于小脑运动学习。然而，目前仍不清楚突触可塑性如何改变绒球中运动学习所依赖的信号处理。一项计算模拟表明，苔藓纤维-颗粒细胞突触中存在的可塑性改善了传入颗粒细胞的与VOR相关的感觉运动信息，而分子层中的可塑性在攀爬纤维教学信号的引导下将该信息存储为记忆。因此，在小脑中多种形式的可塑性中，运动学习和记忆被认为主要由平行纤维-浦肯野细胞突触处的LTD和LTP以及分子中间神经元-浦肯野细胞突触处的反弹增强所诱导。在本研究中，我们重点关注平行纤维-浦肯野细胞突触处的LTD和LTP。基于我们的模拟，我们提出急性VOR运动学习是通过LTP同时增强眼球运动信号和通过LTD抑制前庭信号以增加VOR增益（增益增加学习）来实现的。为了降低VOR增益（增益降低学习），这两个信号以相反的方向进行修改；即，LTD抑制眼球运动信号，而LTP增强前庭信号。
