Cerebellar D1DR-expressing neurons modulate the frontal cortex during timing tasks.
Cerebellar D1DR-expressing neurons modulate the frontal cortex during timing tasks.
复制标题
小脑 D1DR 表达神经元在计时任务期间调节额叶皮层。
DOI：
10.1016/j.nlm.2019.107067
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发表时间：
2020
影响因子：
2.7
通讯作者：
Parker,KrystalL
中科院分区：
文献类型：
--
作者：
Heskje,Jonah;Heslin,Kelsey;DeCorte,BenjaminJ;Walsh,KyleP;Kim,Youngcho;Han,Sangwoo;Carlson,ErikS;Parker,KrystalL
越来越多的证据表明，小脑通过与内侧额叶皮质(MFC)等联想皮质的相互作用，在认知功能中发挥着不可或缺的作用。目前尚不清楚小脑是如何影响额叶皮质的，以及这两个区域之间相互传递的信息类型。啮齿类动物的小脑齿状核或相应的小脑外侧核(LCN)中的一部分神经元表达D1DR，并可能在认知过程中发挥作用。我们研究了药物阻断LCN D1DR如何影响间隔计时任务的表现，并影响额叶皮质的神经元活动。间隔计时需要工作记忆、注意力和计划等执行过程，众所周知，它依赖于额叶皮质和小脑。在我们的间隔计时任务中，雄性大鼠通过按下杠杆来获得水奖励，来表示它们对几秒钟过去时间的估计。我们已经证明，MFC中线索诱发的低频活动爆发引发单个MFC神经元的斜坡活动(即单调的放电率随时间的增加或减少)。这些活动模式与成功的间隔计时性能相关。在这里，我们探索了用D1DR拮抗剂SCH23390阻断右侧LCN D1DR如何影响对侧(左侧)MFC的计时表现和神经活动。我们的结果表明，阻断LCN D1DR会损害一些间隔计时性能的测量。此外，MFC单个单元的斜坡活动显著减弱。这些数据为LCN中的儿茶酚胺如何驱动MFC神经元动力学影响认知功能提供了洞察。
Converging lines of evidence suggest that the cerebellum plays an integral role in cognitive function through its interactions with association cortices like the medial frontal cortex (MFC). It is unknown precisely how the cerebellum influences the frontal cortex and what type of information is reciprocally relayed between these two regions. A subset of neurons in the cerebellar dentate nuclei, or the homologous lateral cerebellar nuclei (LCN) in rodents, express D1 dopamine receptors (D1DRs) and may play a role in cognitive processes. We investigated how pharmacologically blocking LCN D1DRs influences performance in an interval timing task and impacts neuronal activity in the frontal cortex. Interval timing requires executive processes such as working memory, attention, and planning and is known to rely on both the frontal cortex and cerebellum. In our interval timing task, male rats indicated their estimates of the passage of a period of several seconds by making lever presses for a water reward. We have shown that a cue-evoked burst of low-frequency activity in the MFC initiates ramping activity (i.e., monotonic increases or decreases of firing rate over time) in single MFC neurons. These patterns of activity are associated with successful interval timing performance. Here we explored how blocking right LCN D1DRs with the D1DR antagonist SCH23390 influences timing performance and neural activity in the contralateral (left) MFC. Our results indicate that blocking LCN D1DRs impaired some measures of interval timing performance. Additionally, ramping activity of MFC single units was significantly attenuated. These data provide insight into how catecholamines in the LCN may drive MFC neuronal dynamics to influence cognitive function.