Autonomous Purkinje cell activation instructs bidirectional motor learning through evoked dendritic calcium signaling.
Autonomous Purkinje cell activation instructs bidirectional motor learning through evoked dendritic calcium signaling.
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DOI：
10.1038/s41467-021-22405-8
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发表时间：
2021-04-12
影响因子：
16.6
通讯作者：
Christie JM
中科院分区：
文献类型：
--
作者：
Bonnan A;Rowan MMJ;Baker CA;Bolton MM;Christie JM
小脑浦肯野细胞中足以指导运动学习的信号尚未得到系统确定。因此，我们在小鼠中应用光遗传学来自主激发浦肯野细胞，并测量这种活动对可塑性诱导和适应性行为的影响。离体时，表达通道视紫红质 2 的浦肯野细胞的激发会引发树突 Ca2+ 瞬变，高强度刺激会引发树突尖峰，从而进一步促进 Ca2+ 反应。 Channelrhodopsin-2 诱发的 Ca2+ 瞬变增强了共同活动的平行纤维突触；当树突尖峰增强 Ca2+ 反应时，就会发生抑郁症。在体内，当前庭刺激与相对小幅度的浦肯野细胞 Ca2+ 反应配对时，光遗传学浦肯野细胞激活会导致前庭眼反射增益的适应性降低。相反，与大幅度 Ca2+ 反应配对会增加前庭眼反射增益。光遗传学诱导的可塑性和运动适应依赖于内源性大麻素信号传导，表明该途径参与浦肯野细胞 Ca2+ 升高的下游。我们的结果建立了浦肯野细胞 Ca2+ 信号大小、相反极性可塑性诱导和双向运动学习之间的因果关系。平行纤维突触强度的塑性重加权是获得小脑依赖性运动学习的机制。在这里，作者发现 PC 的光遗传学激活产生树突状 Ca2+ 信号，这些信号在体外诱导可塑性，并指导体内一致眼球运动的学习变化。
The signals in cerebellar Purkinje cells sufficient to instruct motor learning have not been systematically determined. Therefore, we applied optogenetics in mice to autonomously excite Purkinje cells and measured the effect of this activity on plasticity induction and adaptive behavior. Ex vivo, excitation of channelrhodopsin-2-expressing Purkinje cells elicits dendritic Ca2+ transients with high-intensity stimuli initiating dendritic spiking that additionally contributes to the Ca2+ response. Channelrhodopsin-2-evoked Ca2+ transients potentiate co-active parallel fiber synapses; depression occurs when Ca2+ responses were enhanced by dendritic spiking. In vivo, optogenetic Purkinje cell activation drives an adaptive decrease in vestibulo-ocular reflex gain when vestibular stimuli are paired with relatively small-magnitude Purkinje cell Ca2+ responses. In contrast, pairing with large-magnitude Ca2+ responses increases vestibulo-ocular reflex gain. Optogenetically induced plasticity and motor adaptation are dependent on endocannabinoid signaling, indicating engagement of this pathway downstream of Purkinje cell Ca2+ elevation. Our results establish a causal relationship among Purkinje cell Ca2+ signal size, opposite-polarity plasticity induction, and bidirectional motor learning. Plastic reweighting of parallel fiber synaptic strength is a mechanism for the acquisition of cerebellum-dependent motor learning. Here, the authors found that optogenetic activation of PCs generates dendritic Ca2+ signals that induce plasticity in vitro and instruct learned changes to coincident eye movements in vivo.
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影响因子：
7.7
作者：
Baker, Christopher A.;Elyadat, Yishai M.;Bolton, M. McLean
通讯作者：
Bolton, M. McLean
影响因子：
5.3
作者：
Heiney, Shane A.;Kim, Jinsook;Medina, Javier F.
通讯作者：
Medina, Javier F.
影响因子：
7.7
作者：
Harmon, Thomas C.;Magaram, Uri;Raman, Indira M.
通讯作者：
Raman, Indira M.
影响因子：
7.7
作者：
Dana, Hod;Mohar, Boaz;Kim, Douglas S.
通讯作者：
Kim, Douglas S.
DOI：
10.1523/jneurosci.0559-08.2008
发表时间：
2008-07-23
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Davie JT;Clark BA;Häusser M
通讯作者：
Häusser M