重新评估 LTD 在小脑运动学习中的作用。
Reevaluating the role of LTD in cerebellar motor learning.
机构信息
Department of Neuroscience, Dr Molewaterplein 50, Erasmus MC, 3015 GE Rotterdam, The Netherlands.
出版信息
Neuron. 2011 Apr 14;70(1):43-50. doi: 10.1016/j.neuron.2011.02.044.
Abstract
Long-term depression at parallel fiber-Purkinje cell synapses (PF-PC LTD) has been proposed to be required for cerebellar motor learning. To date, tests of this hypothesis have sought to interfere with receptors (mGluR1) and enzymes (PKC, PKG, or αCamKII) necessary for induction of PF-PC LTD and thereby determine if cerebellar motor learning is impaired. Here, we tested three mutant mice that target the expression of PF-PC LTD by blocking internalization of AMPA receptors. Using three different cerebellar coordination tasks (adaptation of the vestibulo-ocular reflex, eyeblink conditioning, and locomotion learning on the Erasmus Ladder), we show that there is no motor learning impairment in these mutant mice that lack PF-PC LTD. These findings demonstrate that PF-PC LTD is not essential for cerebellar motor learning.
摘要
长时程抑制在平行纤维-浦肯野细胞突触（PF-PC LTD）被提出是小脑运动学习所必需的。迄今为止，对这一假说的检验试图干扰诱导 PF-PC LTD 所必需的受体（mGluR1）和酶（PKC、PKG 或 αCamKII），从而确定小脑运动学习是否受损。在这里，我们测试了三种突变小鼠，通过阻断 AMPA 受体的内化来靶向 PF-PC LTD 的表达。使用三种不同的小脑协调任务（前庭眼反射的适应、眨眼条件反射和在 Erasmus 梯上的运动学习），我们表明这些缺乏 PF-PC LTD 的突变小鼠没有运动学习障碍。这些发现表明，PF-PC LTD 对于小脑运动学习不是必需的。
相似文献
1
Reevaluating the role of LTD in cerebellar motor learning.重新评估 LTD 在小脑运动学习中的作用。
Neuron. 2011 Apr 14;70(1):43-50. doi: 10.1016/j.neuron.2011.02.044.
2
Computational Theory Underlying Acute Vestibulo-ocular Reflex Motor Learning with Cerebellar Long-Term Depression and Long-Term Potentiation.基于小脑长时程抑制和长时程增强的急性前庭眼反射运动学习的计算理论
Cerebellum. 2017 Aug;16(4):827-839. doi: 10.1007/s12311-017-0857-6.
3
alphaCaMKII Is essential for cerebellar LTD and motor learning.α钙调蛋白激酶II对小脑长时程抑制和运动学习至关重要。
Neuron. 2006 Sep 21;51(6):835-43. doi: 10.1016/j.neuron.2006.08.013.
4
Interneuronal NMDA receptors regulate long-term depression and motor learning in the cerebellum.中间神经元 NMDA 受体调节小脑的长时程抑制和运动学习。
J Physiol. 2019 Feb;597(3):903-920. doi: 10.1113/JP276794. Epub 2018 Nov 24.
5
LTD, RP, and Motor Learning.长期抑郁、反应时和运动学习
Cerebellum. 2016 Feb;15(1):51-53. doi: 10.1007/s12311-015-0698-0.
6
Long-Term Depression of Intrinsic Excitability Accompanied by Synaptic Depression in Cerebellar Purkinje Cells.小脑浦肯野细胞中内在兴奋性的长期抑制伴随着突触抑制
J Neurosci. 2017 Jun 7;37(23):5659-5669. doi: 10.1523/JNEUROSCI.3464-16.2017. Epub 2017 May 11.
7
Reassessment of long-term depression in cerebellar Purkinje cells in mice carrying mutated GluA2 C terminus.对携带突变型GluA2 C末端的小鼠小脑浦肯野细胞中长期抑制的重新评估。
Proc Natl Acad Sci U S A. 2016 Sep 6;113(36):10192-7. doi: 10.1073/pnas.1609957113. Epub 2016 Aug 22.
8
Assessment of Long-term Depression Induction in Adult Cerebellar Slices.成年小脑切片中长时程抑制诱导的评估。
J Vis Exp. 2019 Oct 16(152). doi: 10.3791/59859.
9
Purkinje cell-specific knockout of the protein phosphatase PP2B impairs potentiation and cerebellar motor learning.浦肯野细胞特异性敲除蛋白磷酸酶 PP2B 可损害易化作用和小脑运动学习。
Neuron. 2010 Aug 26;67(4):618-28. doi: 10.1016/j.neuron.2010.07.009.
10
Oculomotor plasticity during vestibular compensation does not depend on cerebellar LTD.前庭代偿过程中的动眼神经可塑性并不依赖于小脑长时程抑制。
J Neurophysiol. 2006 Sep;96(3):1187-95. doi: 10.1152/jn.00045.2006. Epub 2006 May 24.
引用本文的文献
1
GABA, Glx, and GSH in the cerebellum: their role in motor performance and learning across age groups.小脑内的γ-氨基丁酸、谷氨酰胺和谷胱甘肽：它们在各年龄组运动表现和学习中的作用。
Front Aging Neurosci. 2025 Jul 3;17:1626417. doi: 10.3389/fnagi.2025.1626417. eCollection 2025.
2
Purkinje cell models: past, present and future.浦肯野细胞模型：过去、现在与未来。
Front Comput Neurosci. 2024 Jul 10;18:1426653. doi: 10.3389/fncom.2024.1426653. eCollection 2024.
3
Mesoscale simulations predict the role of synergistic cerebellar plasticity during classical eyeblink conditioning.中尺度模拟预测了协同小脑可塑性在经典眨眼条件反射中的作用。
PLoS Comput Biol. 2024 Apr 4;20(4):e1011277. doi: 10.1371/journal.pcbi.1011277. eCollection 2024 Apr.
4
Climbing fibers provide essential instructive signals for associative learning. climbing fibers 为联想学习提供了必不可少的指导信号。
Nat Neurosci. 2024 May;27(5):940-951. doi: 10.1038/s41593-024-01594-7. Epub 2024 Apr 2.
5
The Role of Cerebellar Intrinsic Neuronal Excitability, Synaptic Plasticity, and Perineuronal Nets in Eyeblink Conditioning.小脑内在神经元兴奋性、突触可塑性和神经元周围网在眨眼条件反射中的作用
Biology (Basel). 2024 Mar 21;13(3):200. doi: 10.3390/biology13030200.
6
Interactions between circuit architecture and plasticity in a closed-loop cerebellar system.闭环小脑系统中电路结构与可塑性的相互作用。
Elife. 2024 Mar 7;13:e84770. doi: 10.7554/eLife.84770.
7
Internal models of self-motion: neural computations by the vestibular cerebellum.自身运动的内部模型：前庭小脑的神经计算。
Trends Neurosci. 2023 Nov;46(11):986-1002. doi: 10.1016/j.tins.2023.08.009. Epub 2023 Sep 20.
8
Synaptic Mechanisms of Delay Eyeblink Classical Conditioning: AMPAR Trafficking and Gene Regulation in an In Vitro Model.延迟性眨眼条件反射的突触机制：体外模型中的 AMPAR 运输和基因调控。
Mol Neurobiol. 2023 Dec;60(12):7088-7103. doi: 10.1007/s12035-023-03528-z. Epub 2023 Aug 2.
9
Expression of a Form of Cerebellar Motor Memory Requires Learned Alterations to the Activity of Inhibitory Molecular Layer Interneurons.表达一种小脑运动记忆需要对抑制性分子层中间神经元的活动进行学习性改变。
J Neurosci. 2023 Jan 25;43(4):601-612. doi: 10.1523/JNEUROSCI.0731-22.2022. Epub 2022 Dec 9.
10
Optogenetic activation of mGluR1 signaling in the cerebellum induces synaptic plasticity.小脑内代谢型谷氨酸受体1（mGluR1）信号通路的光遗传学激活可诱导突触可塑性。
iScience. 2022 Dec 17;26(1):105828. doi: 10.1016/j.isci.2022.105828. eCollection 2023 Jan 20.
本文引用的文献
1
Intrinsic plasticity complements long-term potentiation in parallel fiber input gain control in cerebellar Purkinje cells.内在可塑性与长时程增强协同作用，共同调节小脑浦肯野细胞平行纤维输入增益控制。
J Neurosci. 2010 Oct 13;30(41):13630-43. doi: 10.1523/JNEUROSCI.3226-10.2010.
2
Cerebellar molecular layer interneurons - computational properties and roles in learning.小脑分子层中间神经元——计算特性及其在学习中的作用。
Trends Neurosci. 2010 Nov;33(11):524-32. doi: 10.1016/j.tins.2010.08.004. Epub 2010 Sep 24.
3
Purkinje cell-specific knockout of the protein phosphatase PP2B impairs potentiation and cerebellar motor learning.浦肯野细胞特异性敲除蛋白磷酸酶 PP2B 可损害易化作用和小脑运动学习。
Neuron. 2010 Aug 26;67(4):618-28. doi: 10.1016/j.neuron.2010.07.009.
4
Genetic dissection of the function of hindbrain axonal commissures.对后脑轴突连合功能的遗传剖析。
PLoS Biol. 2010 Mar 9;8(3):e1000325. doi: 10.1371/journal.pbio.1000325.
5
Elimination of climbing fiber instructive signals during motor learning.运动学习过程中攀缘纤维指导性信号的消除。
Nat Neurosci. 2009 Sep;12(9):1171-9. doi: 10.1038/nn.2366. Epub 2009 Aug 16.
6
Synaptic inhibition of Purkinje cells mediates consolidation of vestibulo-cerebellar motor learning.浦肯野细胞的突触抑制介导前庭小脑运动学习的巩固。
Nat Neurosci. 2009 Aug;12(8):1042-9. doi: 10.1038/nn.2348. Epub 2009 Jul 5.
7
Mechanisms of potentiation of mossy fiber EPSCs in the cerebellar nuclei by coincident synaptic excitation and inhibition.通过同步突触兴奋和抑制增强小脑核中苔藓纤维兴奋性突触后电流的机制。
J Neurosci. 2008 Oct 15;28(42):10549-60. doi: 10.1523/JNEUROSCI.2061-08.2008.
8
Role of olivary electrical coupling in cerebellar motor learning.橄榄体电耦合在小脑运动学习中的作用。
Neuron. 2008 May 22;58(4):599-612. doi: 10.1016/j.neuron.2008.03.016.
9
alphaCaMKII Is essential for cerebellar LTD and motor learning.α钙调蛋白激酶II对小脑长时程抑制和运动学习至关重要。
Neuron. 2006 Sep 21;51(6):835-43. doi: 10.1016/j.neuron.2006.08.013.
10
Selective engagement of plasticity mechanisms for motor memory storage.用于运动记忆存储的可塑性机制的选择性参与。
Neuron. 2006 Sep 21;51(6):823-34. doi: 10.1016/j.neuron.2006.08.026.
Zotero 插件