Causal role for the subthalamic nucleus in interrupting behavior

Causal role for the subthalamic nucleus in interrupting behavior
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DOI:
10.7554/elife.27689
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发表时间:
2017-07-25
期刊:
影响因子:
7.7
通讯作者:
Hnasko, Thomas S.
Hnasko, Thomas S.
中科院分区:
生物学1区
文献类型:
--
作者:
Fife, Kathryn H.;Gutierrez-Reed, Navarre A.;Hnasko, Thomas S.

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因威胁、冲突信息或意外而停止或暂停是行为的基础。跨物种的证据表明,丘脑底核 (STN) 会被涉及停止或暂停的场景激活,但缺乏 STN 因果性地实现停止或暂停的证据。在这里,我们使用光遗传学激活或抑制小鼠 STN,以测试其假定的因果作用。我们首先证明 STN 的光遗传学刺激会激发其主要投射目标。接下来我们表明,STN 投射神经元的短暂激活足以中断或暂停自我发起的舔舐行为。最后,我们开发了一种用惊喜来中断舔舐的试验,结果表明 STN 抑制降低了惊喜的破坏作用。因此,STN 的激活会打断行为,而阻止 STN 会削弱意外的打断效果。这些结果提供了强有力的证据,证明 STN 对于这种形式的行为反应抑制来说既是必要的也是充分的。
Stopping or pausing in response to threats, conflicting information, or surprise is fundamental to behavior. Evidence across species has shown that the subthalamic nucleus (STN) is activated by scenarios involving stopping or pausing, yet evidence that the STN causally implements stops or pauses is lacking. Here we used optogenetics to activate or inhibit mouse STN to test its putative causal role. We first demonstrated that optogenetic stimulation of the STN excited its major projection targets. Next we showed that brief activation of STN projection neurons was sufficient to interrupt or pause a self-initiated bout of licking. Finally, we developed an assay in which surprise was used to interrupt licking, and showed that STN inhibition reduced the disruptive effect of surprise. Thus STN activation interrupts behavior, and blocking the STN blunts the interruptive effect of surprise. These results provide strong evidence that the STN is both necessary and sufficient for such forms of behavioral response suppression.