Early hypersynchrony in juvenile PINK1(-)/(-) motor cortex is rescued by antidromic stimulation.
Early hypersynchrony in juvenile PINK1(-)/(-) motor cortex is rescued by antidromic stimulation.
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DOI：
10.3389/fnsys.2014.00095
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发表时间：
2014
影响因子：
3
通讯作者：
Hammond C
中科院分区：
文献类型：
--
作者：
Carron R;Filipchuk A;Nardou R;Singh A;Michel FJ;Humphries MD;Hammond C
在帕金森氏病(PD)中，皮质网络显示出增强的同步活动，但这是否先于运动体征尚不清楚。我们在PINK1PARK1−/−小鼠身上研究了这个问题，PINK1PARK6变种是家族性帕金森病的一种遗传啮齿动物模型，在16个月时显示出自发活动受损。我们在幼年(P14-P21)野生型或PINK1−/−小鼠的切片上使用双光子钙成像和全细胞膜片钳技术。我们设计了一个水平倾斜的皮质-丘脑-底核切片，其中皮质和丘脑底核(STN)之间的唯一连接是超直接的皮质-丘脑-底核通路。我们在运动障碍前15个月报告了PINK1、−/−、M1皮质网络过度的相关性和同步性。与野生型网络相比，PINK1−/−M1中相关神经元对的百分比和相关强度更高，同步网络事件涉及的神经元比例更高。这两个特征独立于丘脑-皮质通路，对慢性左旋多巴治疗幼鼠不敏感，但完全被STN高频刺激(HFS)诱发的轴突棘波逆行侵入M1锥体神经元所逆转。我们的研究描述了PINK1−/−皮层的早期过度同步化，并提示皮质中间神经元的逆行激活在网络去同步化中的潜在作用。这种对中间神经元活动的反向效应可能对HFS诱导的网络去同步化具有重要意义。
In Parkinson’s disease (PD), cortical networks show enhanced synchronized activity but whether this precedes motor signs is unknown. We investigated this question in PINK1−/− mice, a genetic rodent model of the PARK6 variant of familial PD which shows impaired spontaneous locomotion at 16 months. We used two-photon calcium imaging and whole-cell patch clamp in slices from juvenile (P14–P21) wild-type or PINK1−/− mice. We designed a horizontal tilted cortico-subthalamic slice where the only connection between cortex and subthalamic nucleus (STN) is the hyperdirect cortico-subthalamic pathway. We report excessive correlation and synchronization in PINK1−/− M1 cortical networks 15 months before motor impairment. The percentage of correlated pairs of neurons and their strength of correlation were higher in the PINK1−/− M1 than in the wild type network and the synchronized network events involved a higher percentage of neurons. Both features were independent of thalamo-cortical pathways, insensitive to chronic levodopa treatment of pups, but totally reversed by antidromic invasion of M1 pyramidal neurons by axonal spikes evoked by high frequency stimulation (HFS) of the STN. Our study describes an early excess of synchronization in the PINK1−/− cortex and suggests a potential role of antidromic activation of cortical interneurons in network desynchronization. Such backward effect on interneurons activity may be of importance for HFS-induced network desynchronization.