UMR 8118, CNRS and Université Paris Descartes, 75006 Paris, France, Center for Theoretical Neuroscience, Columbia University, New York, New York, 10032, Department of Bioengineering, Imperial College London, SW7 2AZ London, United Kingdom.
Netherlands Institute for Neuroscience, Royal Dutch Academy of Arts and Sciences, 1000 GC Amsterdam, The Netherlands, Department of Neuroscience, Erasmus MC, 3015 GD Rotterdam, The Netherlands, Department of Molecular Biology and Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08544, and.
J Neurosci. 2014 May 21;34(21):7203-15. doi: 10.1523/JNEUROSCI.2791-13.2014.
Mechanisms of cerebellar motor learning are still poorly understood. The standard Marr-Albus-Ito theory posits that learning involves plasticity at the parallel fiber to Purkinje cell synapses under control of the climbing fiber input, which provides an error signal as in classical supervised learning paradigms. However, a growing body of evidence challenges this theory, in that additional sites of plasticity appear to contribute to motor adaptation. Here, we consider phase-reversal training of the vestibulo-ocular reflex (VOR), a simple form of motor learning for which a large body of experimental data is available in wild-type and mutant mice, in which the excitability of granule cells or inhibition of Purkinje cells was affected in a cell-specific fashion. We present novel electrophysiological recordings of Purkinje cell activity measured in naive wild-type mice subjected to this VOR adaptation task. We then introduce a minimal model that consists of learning at the parallel fibers to Purkinje cells with the help of the climbing fibers. Although the minimal model reproduces the behavior of the wild-type animals and is analytically tractable, it fails at reproducing the behavior of mutant mice and the electrophysiology data. Therefore, we build a detailed model involving plasticity at the parallel fibers to Purkinje cells' synapse guided by climbing fibers, feedforward inhibition of Purkinje cells, and plasticity at the mossy fiber to vestibular nuclei neuron synapse. The detailed model reproduces both the behavioral and electrophysiological data of both the wild-type and mutant mice and allows for experimentally testable predictions.
小脑运动学习的机制仍未被充分理解。标准的 Marr-Albus-Ito 理论假设学习涉及到在平行纤维到浦肯野细胞突触的可塑性，这种可塑性受到来自 climbing fiber 输入的控制，该输入提供了一个错误信号，就像在经典的监督学习范式中一样。然而，越来越多的证据挑战了这一理论，因为额外的可塑性位点似乎有助于运动适应。在这里，我们考虑前庭眼反射（VOR）的相位反转训练，这是一种简单的运动学习形式，在野生型和突变小鼠中有大量的实验数据可用，在这些小鼠中，颗粒细胞的兴奋性或浦肯野细胞的抑制以细胞特异性的方式受到影响。我们呈现了在未经训练的野生型小鼠中测量的浦肯野细胞活动的新电生理记录，这些小鼠接受了这种 VOR 适应任务。然后，我们引入了一个最小模型，该模型由借助 climbing fibers 在浦肯野细胞的平行纤维上进行学习组成。虽然最小模型再现了野生型动物的行为，并且在分析上是可处理的，但它无法再现突变型小鼠的行为和电生理数据。因此，我们构建了一个详细的模型，该模型涉及到平行纤维到浦肯野细胞突触的可塑性，该可塑性由 climbing fibers 引导，浦肯野细胞的前馈抑制，以及苔藓纤维到前庭神经核神经元突触的可塑性。详细模型再现了野生型和突变型小鼠的行为和电生理数据，并允许进行可实验验证的预测。
