Chen Gang, Popa Laurentiu S, Wang Xinming, Gao Wangcai, Barnes Justin, Hendrix Claudia M, Hess Ellen J, Ebner Timothy J
Department of Neuroscience, University of Minnesota, Lions Research Building, Room 421, 2001 Sixth Street S.E., Minneapolis, MN 55455, USA.
J Neurophysiol. 2009 Jan;101(1):234-45. doi: 10.1152/jn.90829.2008. Epub 2008 Nov 5.
The tottering mouse is an autosomal recessive disorder involving a missense mutation in the gene encoding P/Q-type voltage-gated Ca2+ channels. The tottering mouse has a characteristic phenotype consisting of transient attacks of dystonia triggered by stress, caffeine, or ethanol. The neural events underlying these episodes of dystonia are unknown. Flavoprotein autofluorescence optical imaging revealed transient, low-frequency oscillations in the cerebellar cortex of anesthetized and awake tottering mice but not in wild-type mice. Analysis of the frequencies, spatial extent, and power were used to characterize the oscillations. In anesthetized mice, the dominant frequencies of the oscillations are between 0.039 and 0.078 Hz. The spontaneous oscillations in the tottering mouse organize into high power domains that propagate to neighboring cerebellar cortical regions. In the tottering mouse, the spontaneous firing of 83% (73/88) of cerebellar cortical neurons exhibit oscillations at the same low frequencies. The oscillations are reduced by removing extracellular Ca2+ and blocking L-type Ca2+ channels. The oscillations are likely generated intrinsically in the cerebellar cortex because they are not affected by blocking AMPA receptors or by electrical stimulation of the parallel fiber-Purkinje cell circuit. Furthermore, local application of an L-type Ca2+ agonist in the tottering mouse generates oscillations with similar properties. The beam-like response evoked by parallel fiber stimulation is reduced in the tottering mouse. In the awake tottering mouse, transcranial flavoprotein imaging revealed low-frequency oscillations that are accentuated during caffeine-induced attacks of dystonia. During dystonia, oscillations are also present in the face and hindlimb electromyographic (EMG) activity that become significantly coherent with the oscillations in the cerebellar cortex. These low-frequency oscillations and associated cerebellar cortical dysfunction demonstrate a novel abnormality in the tottering mouse. These oscillations are hypothesized to be involved in the episodic movement disorder in this mouse model of episodic ataxia type 2.
蹒跚小鼠是一种常染色体隐性疾病，涉及编码P/Q型电压门控Ca2+通道的基因中的错义突变。蹒跚小鼠具有特征性表型，包括由压力、咖啡因或乙醇引发的肌张力障碍短暂发作。这些肌张力障碍发作背后的神经事件尚不清楚。黄素蛋白自发荧光光学成像显示，麻醉和清醒的蹒跚小鼠小脑皮质存在短暂的低频振荡，而野生型小鼠则没有。通过分析频率、空间范围和功率来表征这些振荡。在麻醉小鼠中，振荡的主导频率在0.039至0.078赫兹之间。蹒跚小鼠中的自发振荡组织成高功率域，并传播到相邻的小脑皮质区域。在蹒跚小鼠中，83%（73/88）的小脑皮质神经元的自发放电表现出相同的低频振荡。去除细胞外Ca2+并阻断L型Ca2+通道可减少振荡。这些振荡可能是在小脑皮质内源性产生的，因为它们不受阻断AMPA受体或平行纤维-浦肯野细胞回路电刺激的影响。此外，在蹒跚小鼠中局部应用L型Ca2+激动剂会产生具有相似特性的振荡。在蹒跚小鼠中，平行纤维刺激引起的束状反应减弱。在清醒的蹒跚小鼠中，经颅黄素蛋白成像显示低频振荡在咖啡因诱发的肌张力障碍发作期间会加剧。在肌张力障碍期间，面部和后肢肌电图（EMG）活动中也存在振荡，这些振荡与小脑皮质中的振荡显著相干。这些低频振荡和相关的小脑皮质功能障碍表明蹒跚小鼠存在一种新的异常。据推测，这些振荡与这种发作性共济失调2型小鼠模型中的发作性运动障碍有关。
