Hoogland Tycho M, De Gruijl Jornt R, Witter Laurens, Canto Cathrin B, De Zeeuw Chris I
Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA Amsterdam, the Netherlands.
Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA Amsterdam, the Netherlands.
Curr Biol. 2015 May 4;25(9):1157-65. doi: 10.1016/j.cub.2015.03.009. Epub 2015 Apr 2.
It is a longstanding question in neuroscience how elaborate multi-joint movements are coordinated coherently. Microzones of cerebellar Purkinje cells (PCs) are thought to mediate this coordination by controlling the timing of particular motor domains. However, it remains to be elucidated to what extent motor coordination deficits can be correlated with abnormalities in coherent activity within these microzones and to what extent artificially evoked synchronous activity within PC ensembles can elicit multi-joint motor behavior. To study PC ensemble correlates of limb, trunk, and tail movements, we developed a transparent disk treadmill that allows quantitative readout of locomotion and posture parameters in head-fixed mice and simultaneous cellular-resolution imaging and/or optogenetic manipulation. We show that PC ensembles in the ataxic and dystonic mouse mutant tottering have a reduced level of complex spike co-activation, which is delayed relative to movement onset and co-occurs with prolonged swing duration and reduced phase coupling of limb movements as well as with enlarged deflections of body-axis and tail movements. Using optogenetics to increase simple spike rate in PC ensembles, we find that preferred locomotion and posture patterns can be elicited or perturbed depending on the behavioral state. At rest, preferred sequences of limb movements can be elicited, whereas during locomotion, preferred gait-inhibition patterns are evoked. Our findings indicate that synchronous activation of PC ensembles can facilitate initiation and coordination of limb and trunk movements, presumably by tuning downstream systems involved in the execution of behavioral patterns.
在神经科学领域,一个长期存在的问题是精细的多关节运动是如何连贯协调的。小脑浦肯野细胞(PCs)的微区被认为通过控制特定运动域的时间来介导这种协调。然而,运动协调缺陷在多大程度上与这些微区内的连贯活动异常相关,以及在PC集群中人为诱发的同步活动在多大程度上能够引发多关节运动行为,仍有待阐明。为了研究肢体、躯干和尾巴运动的PC集群相关性,我们开发了一种透明圆盘跑步机,它能够对头固定小鼠的运动和姿势参数进行定量读取,并同时进行细胞分辨率成像和/或光遗传学操作。我们发现,共济失调和张力障碍小鼠突变体蹒跚(tottering)中的PC集群,其复杂峰电位共同激活水平降低,相对于运动开始延迟,并且与肢体运动的摆动持续时间延长、相位耦合减少以及身体轴和尾巴运动的偏斜增大同时出现。利用光遗传学提高PC集群中的简单峰电位发放率,我们发现根据行为状态,可以诱发或扰乱偏好的运动和姿势模式。在休息时,可以诱发偏好的肢体运动序列,而在运动过程中,则会诱发偏好的步态抑制模式。我们的研究结果表明,PC集群的同步激活可以促进肢体和躯干运动的启动和协调,大概是通过调节参与行为模式执行的下游系统来实现的。