Reduced Reach-Related Modulation of Motor Thalamus Neural Activity in a Rat Model of Parkinson's Disease
Reduced Reach-Related Modulation of Motor Thalamus Neural Activity in a Rat Model of Parkinson's Disease
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DOI：
10.1523/jneurosci.0893-14.2014
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发表时间：
2014-11-26
影响因子：
5.3
通讯作者：
Parr-Brownlie, Louise C.
中科院分区：
文献类型：
--
作者：
Bosch-Bouju, Clementine;Smither, Roseanna A.;Parr-Brownlie, Louise C.
运动丘脑（Mthal）是皮质基底神经节（BG）回路中的关键节点，控制运动的复杂认知方面。在帕金森病（PD）中，BG核和皮质中发生神经元活动的深刻变化。由于Mthal位于这两个结构之间，因此Mthal活性的改变被认为是PD运动缺陷发病机制的基础。然而，迄今为止，在帕金森病动物中报告了神经元放电率和模式的不一致变化。此外，尽管在减少的制备物中观察到Mthal神经元的独特放电模式，称为低阈值钙峰爆发（LTS爆发），但它们是否发生或它们在行为动物中的作用仍然未知。我们记录了对照组和单侧6-羟基多巴胺损伤大鼠执行熟练的前肢达到任务的Mthal尖峰活动。我们首次表明，在对照组大鼠的Mthal放电率调制在一个时间上精确的模式，在达到抓movements，与达到结束的时间和低谷之前和之后，它的峰值。我们确定的LTS突发特性的基础上的LTS-样事件。这些都是罕见的，但也调制，发病率下降后，达到结束。帕金森病大鼠放电频率和LTS样事件的抑制性调制被取消。这些数据证实，黑质纹状体多巴胺耗竭是伴随着深刻的和具体的赤字运动相关的Mthal活动。这些变化将严重损害Mthal对运动皮层运动程序发育的贡献，可能是PD运动缺陷的重要因素。
Motor thalamus (Mthal) is a key node in the corticobasal ganglia (BG) loop that controls complex, cognitive aspects of movement. In Parkinson's disease (PD), profound alterations in neuronal activity occur in BG nuclei and cortex. Because Mthal is located between these two structures, altered Mthal activity has been assumed to underlie the pathogenesis of PD motor deficits. However, to date, inconsistent changes in neuronal firing rate and pattern have been reported in parkinsonian animals. Moreover, although a distinct firing pattern of Mthal neurons, called low-threshold calcium spike bursts (LTS bursts), is observed in reduced preparations, it remains unknown whether they occur or what their role might be in behaving animals. We recorded Mthal spiking activity in control and unilateral 6-hydroxydopamine lesioned rats performing a skilled forelimb-reaching task. We show for the first time that Mthal firing rate in control rats is modulated in a temporally precise pattern during reach-to-grasp movements, with a peak at the time of the reach-end and troughs just before and after it. We identified LTS-like events on the basis of LTS burst characteristics. These were rare, but also modulated, decreasing in incidence just after reach-end. The inhibitory modulations in firing rate and LTS-like events were abolished in parkinsonian rats. These data confirm that nigrostriatal dopamine depletion is accompanied by profound and specific deficits in movement-related Mthal activity. These changes would severely impair Mthal contributions to motor program development in motor cortex and are likely to be an important factor underlying the movement deficits of PD.