Motor skills mediated through cerebellothalamic tracts projecting to the central lateral nucleus
Motor skills mediated through cerebellothalamic tracts projecting to the central lateral nucleus
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DOI：
10.1186/s13041-019-0431-x
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发表时间：
2019-02-08
期刊：
影响因子：
3.6
通讯作者：
Kobayashi, Kazuto
中科院分区：
文献类型：
--
作者：
Sakayori, Nobuyuki;Kato, Shigeki;Kobayashi, Kazuto
小脑通过与许多其他大脑区域的交流来调节复杂的动物行为，如运动控制和空间识别。小脑投射的主要目标是丘脑区域，包括腹前核（VA）和腹外侧核（VL）。另一个丘脑目标是中央外侧核（CL），它主要接受来自小脑齿状核（DN）的神经支配。虽然以往的电生理研究表明CL作为小脑功能的中继，但小脑丘脑束投射到CL介导的行为功能种类尚不清楚。本研究采用免疫毒素（IT）靶向技术结合神经元特异性逆行标记技术，选择性消除小鼠小脑丘脑束。我们证实，IT治疗选择性地减少了DN中的神经元数量。这些接受过it治疗的小鼠表现出正常的地上运动，没有共济失调行为。然而，这些神经元的消除损害了旋转杆试验中的运动协调和伸展试验中的前肢运动。在地点识别、Morris水迷宫和t迷宫测试中，空间信息加工的习得完整，变化灵活。尽管神经束标记表明存在通往VA/VL复合体吻侧的DN-CL通路的轴突侧枝，但吻侧VA/VL的兴奋性病变未显示出运动协调性或前肢到达性的任何显著改变，表明运动技能功能不需要连接VL/VA复合体的轴突分支。综上所述，我们的数据强调，投射到前皮层的小脑丘脑束在运动技能的控制中发挥关键作用，包括运动协调和前肢伸展，但不是空间识别及其灵活性。
The cerebellum regulates complex animal behaviors, such as motor control and spatial recognition, through communication with many other brain regions. The major targets of the cerebellar projections are the thalamic regions including the ventroanterior nucleus (VA) and ventrolateral nucleus (VL). Another thalamic target is the central lateral nucleus (CL), which receives the innervations mainly from the dentate nucleus (DN) in the cerebellum. Although previous electrophysiological studies suggest the role of the CL as the relay of cerebellar functions, the kinds of behavioral functions mediated by cerebellothalamic tracts projecting to the CL remain unknown. Here, we used immunotoxin (IT) targeting technology combined with a neuron-specific retrograde labeling technique, and selectively eliminated the cerebellothalamic tracts of mice. We confirmed that the number of neurons in the DN was selectively decreased by the IT treatment. These IT-treated mice showed normal overground locomotion with no ataxic behavior. However, elimination of these neurons impaired motor coordination in the rotarod test and forelimb movement in the reaching test. These mice showed intact acquisition and flexible change of spatial information processing in the place discrimination, Morris water maze, and T-maze tests. Although the tract labeling indicated the existence of axonal collaterals of the DN-CL pathway to the rostral part of the VA/VL complex, excitatory lesion of the rostral VA/VL did not show any significant alterations in motor coordination or forelimb reaching, suggesting no requirement of axonal branches connecting to the VL/VA complex for motor skill function. Taken together, our data highlight that the cerebellothalamic tracts projecting to the CL play a key role in the control of motor skills, including motor coordination and forelimb reaching, but not spatial recognition and its flexibility.