Supervised learning depends on instructive signals that shape the output of neural circuits to support learned changes in behavior. Climbing fiber (CF) inputs to the cerebellar cortex represent one of the strongest candidates in the vertebrate brain for conveying neural instructive signals. However, recent studies have shown that Purkinje cell stimulation can also drive cerebellar learning and the relative importance of these two neuron types in providing instructive signals for cerebellum-dependent behaviors remains unresolved. In the present study we used cell-type-specific perturbations of various cerebellar circuit elements to systematically evaluate their contributions to delay eyeblink conditioning in mice. Our findings reveal that, although optogenetic stimulation of either CFs or Purkinje cells can drive learning under some conditions, even subtle reductions in CF signaling completely block learning to natural stimuli. We conclude that CFs and corresponding Purkinje cell complex spike events provide essential instructive signals for associative cerebellar learning.

监督学习依赖于指导性信号，这些信号塑造神经回路的输出以支持习得的行为变化。小脑皮层的攀爬纤维（CF）输入代表了脊椎动物大脑中传递神经指导信号的最强候选者之一。然而，最近的研究表明，浦肯野细胞刺激也可以驱动小脑学习，而这两种神经元类型在为小脑依赖性行为提供指导信号方面的相对重要性仍未得到解决。在本研究中，我们使用各种小脑回路元件的细胞类型特异性扰动来系统地评估它们对延迟小鼠眨眼调节的贡献。我们的研究结果表明，虽然 CF 或浦肯野细胞的光遗传学刺激可以在某些条件下驱动学习，但即使 CF 信号的轻微减少也会完全阻止对自然刺激的学习。我们得出的结论是，CF 和相应的浦肯野细胞复合体尖峰事件为联想小脑学习提供了重要的指导信号。