Long-term Potentiation of Inhibitory Synaptic Transmission onto Cerebellar Purkinje Neurons Contributes to Adaptation of Vestibulo-Ocular Reflex
Long-term Potentiation of Inhibitory Synaptic Transmission onto Cerebellar Purkinje Neurons Contributes to Adaptation of Vestibulo-Ocular Reflex
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DOI：
10.1523/jneurosci.0793-13.2013
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发表时间：
2013-10
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影响因子：
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通讯作者：
Shinsuke Tanaka;Shin-ya Kawaguchi;G. Shioi;T. Hirano
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文献类型：
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作者：
Shinsuke Tanaka;Shin-ya Kawaguchi;G. Shioi;T. Hirano
小脑的突触可塑性被认为有助于运动学习。特别是浦肯野神经元（PN）兴奋性突触平行纤维（PF）的长期抑制（LTD）作为运动学习的主要细胞机制引起了神经科学家的广泛关注。相比之下，可塑性在小脑抑制性突触中的作用在体内仍然未知。在这里，我们研究了长期增强gaba能突触在PN上的传递的作用，即所谓的反弹增强（RP）。先前的研究表明，RP需要GABAA受体与GABAA受体相关蛋白（GABARAP）结合，并且阻断这种结合的肽抑制RP的诱导。为了解决RP的功能作用，我们利用pn特异性L7启动子在PNs中选择性地表达该肽与荧光蛋白融合的转基因小鼠。这些小鼠没有表现出RP，尽管它们没有显示出微型IPSCs的基本振幅或频率的变化。转基因小鼠的小脑大体形态、LTD或其他兴奋性突触特性或PNs的固有兴奋性均未出现异常。接下来，我们试图通过检查眼球反射来评估他们的运动控制和学习能力。转基因小鼠的前庭-眼反射和光动力学反应的基本动力学特性及其适应性均正常。相比之下，转基因小鼠在前庭-眼反射（一种小脑依赖的运动学习模式）的适应方面表现出缺陷。这些结果共同表明，RP有助于某种类型的运动学习。
Synaptic plasticity in the cerebellum is thought to contribute to motor learning. In particular, long-term depression (LTD) at parallel fiber (PF) to Purkinje neuron (PN) excitatory synapses has attracted much attention of neuroscientists as a primary cellular mechanism for motor learning. In contrast, roles of plasticity at cerebellar inhibitory synapses in vivo remain unknown. Here, we have investigated the roles of long-lasting enhancement of transmission at GABAergic synapses on a PN that is known as rebound potentiation (RP). Previous studies demonstrated that binding of GABAA receptor with GABAA receptor-associated protein (GABARAP) is required for RP, and that a peptide that blocks this binding suppresses RP induction. To address the functional roles of RP, we generated transgenic mice that express this peptide fused to a fluorescent protein selectively in PNs using the PN-specific L7 promoter. These mice failed to show RP, although they showed no changes in the basal amplitude or frequency of miniature IPSCs. The transgenic mice also showed no abnormality in gross cerebellar morphology, LTD, or other excitatory synaptic properties, or intrinsic excitability of PNs. Next, we attempted to evaluate their motor control and learning ability by examining reflex eye movements. The basal dynamic properties of the vestibulo-ocular reflex and optokinetic response, and adaptation of the latter, were normal in the transgenic mice. In contrast, the transgenic mice showed defects in the adaptation of vestibulo-ocular reflex, a model paradigm of cerebellum-dependent motor learning. These results together suggest that RP contributes to a certain type of motor learning.