División de Neurociencias, Universidad Pablo de Olavide, Sevilla, Spain.
PLoS One. 2012;7(4):e36184. doi: 10.1371/journal.pone.0036184. Epub 2012 Apr 26.
In vitro studies have supported the occurrence of cerebellar long-term depression (LTD), an interaction between the parallel fibers and Purkinje cells (PCs) that requires the combined activation of the parallel and climbing fibers. To demonstrate the existence of LTD in alert animals, we investigated the plasticity of local field potentials (LFPs) evoked by electrical stimulation of the whisker pad. The recorded LFP showed two major negative waves corresponding to trigeminal (broken into the N2 and N3 components) and cortical responses. PC unitary extracellular recording showed that N2 and N3 occurred concurrently with PC evoked simple spikes, followed by an evoked complex spike. Polarity inversion of the N3 component at the PC level and N3 amplitude reduction after electrical stimulation of the parallel fiber volley applied on the surface of the cerebellum 2 ms earlier strongly suggest that N3 was related to the parallel fiber-PC synapse activity. LFP measurements elicited by single whisker pad stimulus were performed before and after trains of electrical stimuli given at a frequency of 8 Hz for 10 min. We demonstrated that during this later situation, the stimulation of the PC by parallel and climbing fibers was reinforced. After 8-Hz stimulation, we observed long-term modifications (lasting at least 30 min) characterized by a specific decrease of the N3 amplitude accompanied by an increase of the N2 and N3 latency peaks. These plastic modifications indicated the existence of cerebellar LTD in alert animals involving both timing and synaptic modulations. These results corroborate the idea that LTD may underlie basic physiological functions related to calcium-dependent synaptic plasticity in the cerebellum.
在体外研究中已经证实小脑长时程抑制（ LTD ）的存在，这是平行纤维和浦肯野细胞（ PCs ）之间的相互作用，需要平行纤维和 climbing 纤维的联合激活。为了在警觉动物中证明 LTD 的存在，我们研究了电刺激胡须垫诱发的局部场电位（ LFPs ）的可塑性。记录的 LFP 显示了两个主要的负波，对应于三叉神经（分为 N2 和 N3 成分）和皮质反应。PC 单位细胞外记录显示，N2 和 N3 与 PC 诱发的简单峰同时发生，随后是诱发的复杂峰。在小脑表面施加的平行纤维爆发的电刺激 2 ms 前，N3 成分在 PC 水平上的极性反转和 N3 振幅减小强烈表明 N3 与平行纤维-PC 突触活动有关。在单个胡须垫刺激下进行的 LFPs 测量在电刺激 8 Hz 10 min 的前后进行。我们证明，在这种后期情况下，平行纤维和 climbing 纤维对 PC 的刺激得到了加强。在 8-Hz 刺激后，我们观察到长期的变化（至少持续 30 分钟），特征是 N3 振幅的特定减小伴随着 N2 和 N3 潜伏期峰值的增加。这些塑性变化表明在警觉动物中存在小脑 LTD ，涉及时间和突触调节。这些结果证实了 LTD 可能是小脑钙依赖性突触可塑性相关的基本生理功能的基础。
