Scopolamine and Medial Frontal Stimulus-Processing during Interval Timing.
Scopolamine and Medial Frontal Stimulus-Processing during Interval Timing.
复制标题
间隔计时期间的东莨菪碱和内侧额叶刺激处理。
DOI：
10.1016/j.neuroscience.2019.07.004
复制
发表时间：
2019
期刊：
影响因子：
3.3
通讯作者：
Narayanan,NandakumarS
中科院分区：
文献类型：
--
作者：
Zhang,Qiang;Jung,Dennis;Larson,Travis;Kim,Youngcho;Narayanan,NandakumarS
神经退行性疾病如帕金森病（PD）、路易体痴呆（DLB）和阿尔茨海默病（AD）涉及基底前脑中胆碱能神经元的损失。在这里，我们调查胆碱能功能障碍如何影响额叶皮层在间隔时间，一个过程中，可以受损的PD和AD患者。间隔计时要求参与者通过做出运动反应来估计几秒的间隔，并且取决于内侧额叶皮层（MFC），其由基底前脑胆碱能投射丰富地支配。过去的工作表明，东莨菪碱，毒蕈碱胆碱能受体拮抗剂，可靠地损害间隔计时。我们测试的假设，东莨菪碱会减弱时间相关的斜坡，在MFC的时间处理的一个关键形式。我们记录了8只小鼠在执行12秒固定间隔计时任务，这是由东莨菪碱的管理受损的神经元合奏。与过去的研究一致，东莨菪碱损害了时间。令我们惊讶的是，我们发现，与时间相关的斜坡是不变的，但刺激相关的活动增强MFC。主成分分析显示，与时间相关的斜坡组件没有一致的变化，但确实显示了更高的组件的变化。两者合计，这些数据表明，东莨菪碱改变刺激处理，而不是在MFC的时间处理。这些数据可以帮助理解胆碱能功能障碍如何影响PD，DLB和AD等疾病的皮质回路。
Neurodegenerative diseases such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and Alzheimer's disease (AD) involve loss of cholinergic neurons in the basal forebrain. Here, we investigate how cholinergic dysfunction impacts the frontal cortex during interval timing, a process that can be impaired in PD and AD patients. Interval timing requires participants to estimate an interval of several seconds by making a motor response, and depends on the medial frontal cortex (MFC), which is richly innervated by basal forebrain cholinergic projections. Past work has shown that scopolamine, a muscarinic cholinergic receptor antagonist, reliably impairs interval timing. We tested the hypothesis that scopolamine would attenuate time-related ramping, a key form of temporal processing in the MFC. We recorded neuronal ensembles from eight mice during performance of a 12-s fixed-interval timing task, which was impaired by the administration of scopolamine. Consistent with past work, scopolamine impaired timing. To our surprise, we found that time-related ramping was unchanged, but stimulus-related activity was enhanced in the MFC. Principal component analyses revealed no consistent changes in time-related ramping components, but did reveal changes in higher components. Taken together, these data indicate that scopolamine changes stimulus processing rather than temporal processing in the MFC. These data could help understand how cholinergic dysfunction affects cortical circuits in diseases such as PD, DLB, and AD.