Role of granule-cell transmission in memory trace of cerebellum-dependent optokinetic motor learning
Role of granule-cell transmission in memory trace of cerebellum-dependent optokinetic motor learning
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DOI：
10.1073/pnas.1402546111
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发表时间：
2014-03
期刊：
影响因子：
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通讯作者：
N. Wada;K. Funabiki;S. Nakanishi
中科院分区：
文献类型：
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作者：
N. Wada;K. Funabiki;S. Nakanishi
浦肯野细胞和前庭核接受视动和视网膜滑动信号，诱导视动运动学习。通过选择性和可逆性阻断颗粒细胞向浦肯野细胞的传递，研究了小脑多回路在适应性视动反应（OKR）中的作用。这种阻断消除了短期和长期的OKR适应，但适应性OKR立即诱导时，颗粒细胞传输恢复在预先训练的，适应性OKR阴性小鼠。眼运动的电刺激的绒球是升高的长期，但不是短期的OKR训练。在适应性OKR阴性小鼠中，同时的绒球和OKR刺激产生正常的OKR适应。这项研究表明，前庭核作为一个关键的电路负责形成和存储的OKR适应。视动反应适应（OKR）是一种通过周围视野的重复运动而增强的眼球运动，代表了小脑依赖性运动学习的原型。浦肯野细胞和前庭核（VN）分别通过苔藓纤维颗粒细胞通路和攀爬纤维投射接收视动和视网膜滑动信号。为了探索OKR适应的神经回路和机制，我们采用了可逆的神经传递阻断（RNB）技术，其中颗粒细胞传递到浦肯野细胞被多西环素依赖性表达的传递阻断破伤风毒素颗粒细胞选择性和可逆地阻断。阻断颗粒细胞的输入取消了短期和长期OKR适应诱导的重复OKR训练，但正常水平的两个反应立即在预先训练的RNB小鼠的OKR再训练，一旦颗粒细胞的传输已经恢复。重要的是，在适应性OKR阴性RNB小鼠中，由小脑焦点的电刺激引起的眼球运动通过长期而不是短期OKR训练而升高。此外，当适应性OKR阴性RNB小鼠的绒球与OKR刺激同相电兴奋时，这些小鼠表现出长期的适应性OKR。这些结果表明，会聚信息的VN是至关重要的收购和存储的长期OKR适应与联合行动的浦肯野细胞OKR的表达。有趣的是，与条件性眨眼记忆相反，一旦获得自适应长期OKR的表达并没有被颗粒细胞传递的阻断所废除，这表明不同形式的神经可塑性将在不同形式的小脑依赖性运动学习中发挥作用。
Significance Purkinje cells and vestibular nuclei receive optokinetic and retinal slip signals that induce optokinetic motor learning. The role of multiple cerebellar circuits in the adaptive optokinetic response (OKR) was investigated by selective and reversible blockade of granule-cell transmission to Purkinje cells. This blockade abrogated both short-term and long-term OKR adaptation, but adaptive OKRs were immediately induced when the granule-cell transmission was recovered in pretrained, adaptive OKR-negative mice. Eye movement by electrical stimulation of the flocculus was elevated by long-term but not by short-term OKR training. Simultaneous flocculus and OKR stimulation produced normal OKR adaptation in adaptive OKR-negative mice. This study demonstrates that vestibular nuclei serve as a critical circuit responsible for formation and storage of OKR adaptation. Adaptation of the optokinetic response (OKR) is an eye movement enhanced by repeated motion of a surrounding visual field and represents a prototype of cerebellum-dependent motor learning. Purkinje cells and vestibular nuclei (VN) receive optokinetic and retinal slip signals via the mossy fiber-granule cell pathway and climbing-fiber projections, respectively. To explore the neural circuits and mechanisms responsible for OKR adaptation, we adopted the reversible neurotransmission-blocking (RNB) technique, in which granule-cell transmission to Purkinje cells was selectively and reversibly blocked by doxycycline-dependent expression of transmission-blocking tetanus toxin in granule cells. Blockade of granule-cell inputs abolished both short-term and long-term OKR adaptation induced by repeated OKR training, but normal levels of both responses were immediately evoked in the pretrained RNB mice by OKR retraining once granule-cell transmission had recovered. Importantly, eye movement elicited by electrical stimulation of the cerebellar focculus was elevated by long-term but not by short-term OKR training in adaptive OKR-negative RNB mice. Furthermore, when the flocculus of adaptive OKR-negative RNB mice was electrically excited in-phase with OKR stimulation, these mice exhibited long-term adaptive OKR. These results indicate that convergent information to the VN was critical for acquisition and storage of long-term OKR adaptation with conjunctive action of Purkinje cells for OKR expression. Interestingly, in contrast to conditioned eyeblink memory, the expression of once acquired adaptive long-term OKR was not abrogated by blockade of granule-cell transmission, suggesting that distinct forms of neural plasticity would operate in different forms of cerebellum-dependent motor learning.