Selective Neural Pathway Targeting Reveals Key Roles of Thalamostriatal Projection in the Control of Visual Discrimination
Selective Neural Pathway Targeting Reveals Key Roles of Thalamostriatal Projection in the Control of Visual Discrimination
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DOI：
10.1523/jneurosci.4005-11.2011
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发表时间：
2011-11-23
影响因子：
5.3
通讯作者：
Kobayashi, Kazuto
中科院分区：
文献类型：
--
作者：
Kato, Shigeki;Kuramochi, Masahito;Kobayashi, Kazuto
背侧纹状体接收来自不同大脑区域的会聚兴奋性输入，包括大脑皮层和板内/中线丘脑核，并介导有助于工具性运动动作的学习过程。然而，在这些学习过程中的纹状体输入通路的作用仍然不确定。我们开发了一种新的策略，以针对特定的神经通路，并应用此策略研究行为的作用，从束旁核（PF）和投射到背外侧纹状体的途径。将编码重组免疫毒素（IT）受体的高效逆行基因转移载体注射到小鼠背外侧纹状体中，以在支配纹状体的神经元中表达受体。IT治疗到PF的载体注射的动物引起PF衍生的丘脑纹状体通路的神经元的选择性消除。消除这一途径损害了响应选择的准确性和延迟的运动反应在收购的视觉线索依赖的歧视任务。当学习获得后诱发通路消除时，它干扰了任务执行中的反应准确性，而反应时没有明显变化。消除并不影响自发运动，甲基苯丙胺诱导的多动症，运动技能学习，需要背侧纹状体的功能。这些结果表明，来自PF的丘脑-纹状体投射在识别学习的获得和执行中起着重要的作用。视觉辨别的通路要求的时间差异表明丘脑-纹状体通路在调节学习运动动作的反应时间中具有阶段特异性作用。
The dorsal striatum receives converging excitatory inputs from diverse brain regions, including the cerebral cortex and the intralaminar/midline thalamic nuclei, and mediates learning processes contributing to instrumental motor actions. However, the roles of each striatal input pathway in these learning processes remain uncertain. We developed a novel strategy to target specific neural pathways and applied this strategy for studying behavioral roles of the pathway originating from the parafascicular nucleus (PF) and projecting to the dorsolateral striatum. A highly efficient retrograde gene transfer vector encoding the recombinant immunotoxin (IT) receptor was injected into the dorsolateral striatum in mice to express the receptor in neurons innervating the striatum. IT treatment into the PF of the vector-injected animals caused a selective elimination of neurons of the PF-derived thalamostriatal pathway. The elimination of this pathway impaired the response selection accuracy and delayed the motor response in the acquisition of a visual cue-dependent discrimination task. When the pathway elimination was induced after learning acquisition, it disturbed the response accuracy in the task performance with no apparent change in the response time. The elimination did not influence spontaneous locomotion, methamphetamine-induced hyperactivity, and motor skill learning that demand the function of the dorsal striatum. These results demonstrate that thalamostriatal projection derived from the PF plays essential roles in the acquisition and execution of discrimination learning in response to sensory stimulus. The temporal difference in the pathway requirement for visual discrimination suggests a stage-specific role of thalamostriatal pathway in the modulation of response time of learned motor actions.