Moscato Letizia, Montagna Ileana, De Propris Licia, Tritto Simona, Mapelli Lisa, D'Angelo Egidio
Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
Brain Connectivity Center, C. Mondino National Neurological Institute, Pavia, Italy.
Front Cell Neurosci. 2019 Mar 6;13:84. doi: 10.3389/fncel.2019.00084. eCollection 2019.
The deep cerebellar nuclei (DCN) have been suggested to play a critical role in sensorimotor learning and some forms of long-term synaptic plasticity observed have been proposed as a possible substrate. However, till now it was not clear whether and how DCN neuron responses manifest long-lasting changes . Here, we have characterized DCN unit responses to tactile stimulation of the facial area in anesthetized mice and evaluated the changes induced by theta-sensory stimulation (TSS), a 4 Hz stimulation pattern that is known to induce plasticity in the cerebellar cortex . DCN units responded to tactile stimulation generating bursts and pauses, which reflected combinations of excitatory inputs most likely relayed by mossy fiber collaterals, inhibitory inputs relayed by Purkinje cells, and intrinsic rebound firing. Interestingly, initial bursts and pauses were often followed by stimulus-induced oscillations in the peri-stimulus time histograms (PSTH). TSS induced long-lasting changes in DCN unit responses. Spike-related potentiation and suppression (SR-P and SR-S), either in units initiating the response with bursts or pauses, were correlated with stimulus-induced oscillations. Fitting with resonant functions suggested the existence of peaks in the theta-band (burst SR-P at 9 Hz, pause SR-S at 5 Hz). Optogenetic stimulation of the cerebellar cortex altered stimulus-induced oscillations suggesting that Purkinje cells play a critical role in the circuits controlling DCN oscillations and plasticity. This observation complements those reported before on the granular and molecular layers supporting the generation of multiple distributed plasticities in the cerebellum following naturally patterned sensory entrainment. The unique dependency of DCN plasticity on circuit oscillations discloses a potential relationship between cerebellar learning and activity patterns generated in the cerebellar network.
深部小脑核团（DCN）被认为在感觉运动学习中起关键作用，并且有人提出所观察到的某些形式的长期突触可塑性可能是其潜在基础。然而，到目前为止，尚不清楚DCN神经元反应是否以及如何表现出持久变化。在此，我们对麻醉小鼠面部区域触觉刺激的DCN单位反应进行了特征描述，并评估了由θ-感觉刺激（TSS）诱导的变化，TSS是一种已知能在小脑皮质诱导可塑性的4Hz刺激模式。DCN单位对触觉刺激产生爆发和停顿反应，这反映了最有可能由苔藓纤维侧支传递的兴奋性输入、浦肯野细胞传递的抑制性输入以及内在反弹放电的组合。有趣的是，在刺激周围时间直方图（PSTH）中，最初的爆发和停顿之后常常伴随着刺激诱导的振荡。TSS诱导了DCN单位反应的持久变化。在以爆发或停顿启动反应的单位中，与刺激相关的增强和抑制（SR-P和SR-S）与刺激诱导的振荡相关。与共振函数拟合表明在θ波段存在峰值（爆发SR-P在9Hz，停顿SR-S在5Hz）。对小脑皮质的光遗传学刺激改变了刺激诱导的振荡，表明浦肯野细胞在控制DCN振荡和可塑性的回路中起关键作用。这一观察结果补充了之前关于颗粒层和分子层的报道，支持在自然模式的感觉夹带后小脑产生多种分布式可塑性。DCN可塑性对回路振荡的独特依赖性揭示了小脑学习与小脑网络中产生的活动模式之间的潜在关系。
