Department of Neuroscience, Erasmus MC, 3000 DR Rotterdam, The Netherlands.
Neuron. 2013 May 22;78(4):700-13. doi: 10.1016/j.neuron.2013.03.018. Epub 2013 May 2.
The cerebellum fine-tunes motor activity via its Purkinje cell output. Purkinje cells produce two different types of spikes, complex spikes and simple spikes, which often show reciprocal activity: a periodical increase in complex spikes is associated with a decrease in simple spikes, and vice versa. This reciprocal firing is thought to be essential for coordinated motor behavior, yet how it is accomplished is debated. Here, we show in Ptf1a::cre;Robo3(lox/lox) mice that selectively rerouting the climbing fibers from a contralateral to an ipsilateral projection reversed the complex-spike modulation during sensory stimulation. Strikingly, modulation of simple spikes, which is supposed to be controlled by mossy fibers, reversed as well. Climbing fibers enforce this reciprocity in part by influencing activity of inhibitory interneurons, because the phase of their activity was also converted. Ptf1a::cre;Robo3(lox/lox) mice showed severe ataxia highlighting that climbing fiber input and its impact on reciprocity of Purkinje cell firing play an important role in motor coordination.
小脑通过其浦肯野细胞输出精细地调节运动活动。浦肯野细胞产生两种不同类型的尖峰，即复杂尖峰和简单尖峰，它们通常表现出相互的活动：复杂尖峰的周期性增加与简单尖峰的减少相关，反之亦然。这种相互放电被认为对于协调的运动行为至关重要，但它是如何实现的还存在争议。在这里，我们在 Ptf1a::cre;Robo3(lox/lox) 小鼠中表明，选择性地将 climbing fibers 从对侧重新路由到同侧投射，逆转了感觉刺激期间的复杂尖峰调制。引人注目的是， supposed 由 mossy fibers 控制的简单尖峰的调制也发生了逆转。Climbing fibers 通过影响抑制性中间神经元的活动来加强这种相互作用，因为它们的活动相位也被转换了。Ptf1a::cre;Robo3(lox/lox) 小鼠表现出严重的共济失调，突出表明 climbing fiber 输入及其对浦肯野细胞放电的相互作用在运动协调中起着重要作用。
