Striatal Low-Threshold Spiking Interneurons Regulate Goal-Directed Learning.

Striatal Low-Threshold Spiking Interneurons Regulate Goal-Directed Learning.
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DOI:
10.1016/j.neuron.2019.04.016
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发表时间:
2019-07-03
期刊:
影响因子:
16.2
通讯作者:
Fuccillo MV
Fuccillo MV
中科院分区:
医学1区
文献类型:
--
作者:
Holly EN;Davatolhagh MF;Choi K;Alabi OO;Vargas Cifuentes L;Fuccillo MV

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背内侧纹状体(DMS)在运动控制和奖励处理中发挥着至关重要的作用,但具体的神经回路介质却知之甚少。最近的证据强调了局部纹状体回路中低阈值尖峰中间神经元(LTSI)的广泛连接性;然而,LTSI 的体内功能在很大程度上仍未得到探索。我们采用光纤光度测定法来评估一系列 DMS 介导的行为中的 LTSI 钙活性,发现在目标导向学习过程中下调的特定奖励相关活动。使用两种机制上不同的操作,我们证明了 LTSI 活动的下调对于获取新的意外事件至关重要,但对于它们的修改却不是。相反,持续的 LTSI 激活会减慢仪器学习。对快速尖峰中间神经元的类似操作没有重现这些效应,这意味着 LTSI 具有特定功能。最后,我们揭示了 LTSI 的 γ-氨基丁酸 (GABA) 能功能在学习中的作用。总之,我们的数据为纹状体中间神经元亚类作为目标导向学习的重要守门人提供了新的见解。背内侧纹状体低阈值尖峰中间神经元(LTSI)在行为中的功能作用在很大程度上尚未被探索。霍莉等人。表明 LTSI 具有奖励与结果相关的活动,该活动随着目标导向的学习而减少并因果调节。
The dorsomedial striatum (DMS) is critically involved in motor control and reward processing, but the specific neural circuit mediators are poorly understood. Recent evidence highlights the extensive connectivity of low-threshold spiking interneurons (LTSIs) within local striatal circuitry; however, the in vivo function of LTSIs remains largely unexplored. We employed fiber photometry to assess LTSI calcium activity in a range of DMS-mediated behaviors, uncovering specific reward-related activity that is down-modulated during goal-directed learning. Using two mechanistically distinct manipulations, we demonstrated that this down-modulation of LTSI activity is critical for acquisition of novel contingencies, but not for their modification. In contrast, continued LTSI activation slowed instrumental learning. Similar manipulations of fast-spiking interneurons did not reproduce these effects, implying a specific function of LTSIs. Finally, we revealed a role for the γ-aminobutyric acid (GABA)ergic functions of LTSIs in learning. Together, our data provide new insights into this striatal interneuron subclass as important gatekeepers of goal-directed learning. The functional role of dorsomedial striatum low-threshold spiking interneurons (LTSIs) in behavior has been largely unexplored. Holly et al. show that LTSIs have reward outcome-associated activity that decreases with and causally modulates goal-directed learning.
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