Orbitofrontal-striatal potentiation underlies cocaine-induced hyperactivity
Orbitofrontal-striatal potentiation underlies cocaine-induced hyperactivity
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DOI：
10.1038/s41467-020-17763-8
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发表时间：
2020-08-10
影响因子：
16.6
通讯作者：
Kravitz, Alexxai, V
中科院分区：
文献类型：
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作者：
Bariselli, Sebastiano;Miyazaki, Nanami L.;Kravitz, Alexxai, V
精神运动兴奋剂增加纹状体中的多巴胺水平并促进运动；然而，它们对体内纹状体通路功能的影响尚不清楚。一个已经提出的解释这些运动效应的模型表明，刺激剂分别通过激活和抑制直接和间接途径的纹状体神经元来驱动多动。尽管这一假说与多巴胺受体的细胞活动相一致，并得到了光遗传学和化学遗传学研究的支持，但它很少被活体记录所验证。在这里，我们测试了这个模型，并观察到可卡因增加了清醒小鼠纹状体中这两个通路的活动。这些变化与体内多巴胺依赖可卡因诱导的背内侧纹状体(DMS)上游眶前皮质(OFC)输入的增强有关。最后，用高频刺激方案抑制清醒小鼠的OFC-DMS通路，使可卡因诱导的OFC-DMS通路的增强超过可卡因诱导的OFC-DMS通路的增强，并减弱运动敏化的表达，直接将OFC-DMS的增强与可卡因诱导的多动联系起来。精神运动兴奋剂增加纹状体中的多巴胺水平并促进运动，但它们对体内纹状体通路的影响尚不清楚。作者表明，可卡因通过眶前皮质增加清醒小鼠的直接和间接途径纹状体神经元的活动。
Psychomotor stimulants increase dopamine levels in the striatum and promote locomotion; however, their effects on striatal pathway function in vivo remain unclear. One model that has been proposed to account for these motor effects suggests that stimulants drive hyperactivity via activation and inhibition of direct and indirect pathway striatal neurons, respectively. Although this hypothesis is consistent with the cellular actions of dopamine receptors and received support from optogenetic and chemogenetic studies, it has been rarely tested with in vivo recordings. Here, we test this model and observe that cocaine increases the activity of both pathways in the striatum of awake mice. These changes are linked to a dopamine-dependent cocaine-induced strengthening of upstream orbitofrontal cortex (OFC) inputs to the dorsomedial striatum (DMS) in vivo. Finally, depressing OFC-DMS pathway with a high frequency stimulation protocol in awake mice over-powers the cocaine-induced potentiation of OFC-DMS pathway and attenuates the expression of locomotor sensitization, directly linking OFC-DMS potentiation to cocaine-induced hyperactivity. Psychomotor stimulants increase dopamine levels in the striatum and promote locomotion but their effects on striatal pathways in vivo remain unclear. The authors show that cocaine increases the activity of direct and indirect pathway striatal neurons of awake mice via the orbitofrontal cortex.