Corticostriatal Divergent Function in Determining the Temporal and Spatial Properties of Motor Tics
Corticostriatal Divergent Function in Determining the Temporal and Spatial Properties of Motor Tics
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DOI：
10.1523/jneurosci.2770-15.2015
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发表时间：
2015-12-16
影响因子：
5.3
通讯作者：
Bar-Gad, Izhar
中科院分区：
文献类型：
--
作者：
Israelashvili, Michal;Bar-Gad, Izhar
纹状体去抑制导致运动性抽搐的形成，类似于抽动秽语综合征和其他抽搐障碍期间所表达的那些。这些抽搐的空间特性取决于纹状体内局部去抑制的位置，然而，影响抽搐表达的时间特性的因素仍然是未知的。在这里，我们使用微刺激运动皮层的自由行为大鼠纹状体去抑制之前和之后，探索的因素背后的时间个别抽搐。皮层激活通过依赖于输入的频率和幅度的输入的积累过程来确定个体抽搐的时间。由此产生的抽搐和纹状体内的神经元代表性是高度刻板的和独立的皮质活动特性。抽搐的产生受到来自内部纹状体状态的绝对和相对抽搐不应期的限制。因此，抽搐表达的精确时间取决于进入纹状体的兴奋性输入的总和与前一次抽搐的时间之间的相互作用。皮质纹状体功能的数据驱动的计算模型密切复制了抽搐产生的时间特性，并能够根据传入的皮质活动和抽搐历史预测抽搐的时间。这些收敛的实验和计算结果表明，一个明确的功能二分法内的皮质纹状体网络，指向不同的时间（皮质）与空间（纹状体）编码。因此，图雷特综合征和其他抽动障碍的典型的异常纹状体抑制由于异常纹状体网络的皮质激活而导致抽动。
Striatal disinhibition leads to the formation of motor tics resembling those expressed during Tourette syndrome and other tic disorders. The spatial properties of these tics are dependent on the location of the focal disinhibition within the striatum; however, the factors affecting the temporal properties of tic expression are still unknown. Here, we used microstimulation within the motor cortex of freely behaving rats before and after striatal disinhibition to explore the factors underlying the timing of individual tics. Cortical activation determined the timing of individual tics via an accumulation process of inputs that was dependent on the frequency and amplitude of the inputs. The resulting tics and their neuronal representation within the striatum were highly stereotypic and independent of the cortical activity properties. The generation of tics was limited by absolute and relative tic refractory periods that were derived from an internal striatal state. Thus, the precise time of the tic expression depends on the interaction between the summation of incoming excitatory inputs to the striatum and the timing of the previous tic. A data-driven computational model of corticostriatal function closely replicated the temporal properties of tic generation and enabled the prediction of tic timing based on incoming cortical activity and tic history. These converging experimental and computational findings suggest a clear functional dichotomy within the corticostriatal network, pointing to disparate temporal (cortical) versus spatial (striatal) encoding. Thus, the abnormal striatal inhibition typical of Tourette syndrome and other tic disorders results in tics due to cortical activation of the abnormal striatal network.