Department of Neurobiology, Stanford University School of Medicine, Stanford, California.
J Neurophysiol. 2021 Oct 1;126(4):1391-1402. doi: 10.1152/jn.00715.2020. Epub 2021 Aug 4.
The climbing fiber input to the cerebellum conveys instructive signals that can induce synaptic plasticity and learning by triggering complex spikes accompanied by large calcium transients in Purkinje cells. In the cerebellar flocculus, which supports oculomotor learning, complex spikes are driven by image motion on the retina, which could indicate an oculomotor error. In the same neurons, complex spikes also can be driven by nonvisual signals. It has been shown that the calcium transients accompanying each complex spike can vary in amplitude, even within a given cell, therefore, we compared the calcium responses associated with the visual and nonvisual inputs to floccular Purkinje cells. The calcium indicator GCaMP6f was selectively expressed in Purkinje cells, and fiber photometry was used to record the calcium responses from a population of Purkinje cells in the flocculus of awake behaving mice. During visual (optokinetic) stimuli and pairing of vestibular and visual stimuli, the calcium level increased during contraversive retinal image motion. During performance of the vestibulo-ocular reflex in the dark, calcium increased during contraversive head rotation and the associated ipsiverse eye movements. The amplitude of this nonvisual calcium response was comparable to that during conditions with retinal image motion present that induce oculomotor learning. Thus, population calcium responses of Purkinje cells in the cerebellar flocculus to visual and nonvisual input are similar to what has been reported previously for complex spikes, suggesting that multimodal instructive signals control the synaptic plasticity supporting oculomotor learning. It was long known that the climbing fiber input to Purkinje cells in the cerebellar flocculus conveys visual feedback about the accuracy of image-stabilizing oculomotor reflexes. More recently, the same climbing fibers were reported to carry nonvisual signals. Here, we report that both visual and nonvisual inputs can elicit robust calcium responses in the Purkinje cells, suggesting that the instructive signals guiding oculomotor plasticity are multimodal.
小脑的 climbing fiber 输入传递有指导意义的信号，这些信号可以通过在浦肯野细胞中引发伴随大钙瞬变的复杂 spikes，从而诱导突触可塑性和学习。在支持眼球运动学习的小脑绒球中，复杂 spikes 由视网膜上的图像运动驱动，这可能表明眼球运动错误。在相同的神经元中，复杂 spikes 也可以由非视觉信号驱动。已经表明，伴随每个复杂 spikes 的钙瞬变的幅度可以变化，即使在给定的细胞内也是如此，因此，我们比较了与绒球浦肯野细胞的视觉和非视觉输入相关的钙反应。钙指示剂 GCaMP6f 选择性地在浦肯野细胞中表达，并且纤维光度法用于记录在清醒行为小鼠的绒球中的浦肯野细胞群体的钙反应。在视觉（视动）刺激和前庭和视觉刺激配对期间，在对抗性视网膜图像运动期间钙水平增加。在黑暗中进行前庭眼反射时，在对抗性头部旋转和相关的对侧眼球运动期间钙增加。这个非视觉钙反应的幅度与诱导眼球运动学习的存在视网膜图像运动的条件下的幅度相当。因此，小脑绒球中的浦肯野细胞对视觉和非视觉输入的群体钙反应与先前报道的复杂 spikes 相似，表明多模态有指导意义的信号控制支持眼球运动学习的突触可塑性。长期以来，人们一直知道小脑绒球中的浦肯野细胞的 climbing fiber 输入传递有关图像稳定眼球运动反射准确性的视觉反馈。最近，同样的 climbing fibers 被报道携带非视觉信号。在这里，我们报告说，视觉和非视觉输入都可以在浦肯野细胞中引发强烈的钙反应，这表明指导眼球运动可塑性的有指导意义的信号是多模态的。
