The role of the 5-HT2A mediated neurotransmission in behaviour and neuronal dynamics during sleep and waking in mice

5-HT2A介导的神经传递在小鼠睡眠和清醒期间的行为和神经元动力学中的作用

• 批准号: 2271235
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2271235
• 关键词: role; HT2A; mediated; neurotransmission; behaviour

Serotonergic signalling in the brain is important for a broad range of functions - from appetite, thermoregulation, and sleep to anxiety, learning and memory. Studies suggest that manipulations of the serotonergic system can impact the amount and distribution of different vigilance states. For example, a nearly complete elimination of rapid eye movement (REM) sleep, as defined using conventional criteria, was observed after treatment with selective serotonin reuptake inhibitors in both humans and laboratory animals. Surprisingly, the loss of REM sleep does not appear to lead to any overt negative consequences. This suggests either that REM sleep does not have any biological function, or that potentiating serotonergic system results in an occurrence of altered or hybrid states of vigilance that can functionally replace the bona fide REM sleep. If the latter were true, then a key role of the serotonergic system is in controlling the quality, rather than quantity of specific sleep states. The aim of this project is to characterise the effects of 5-HT2A agonists on cortical neural activity and behaviour in freely moving mice. This class of compounds was selected because our preliminary studies suggest their strong REM sleep - suppressing effects in mice. In this study we shall perform chronic electrophysiological recordings from the neocortex in freely moving mice, combined with EMG, accelerometery, positional eye tracking and pupil diameter across spontaneous wakefulness and sleep, as well as during behavioural task performance during and after administration of psilocin and other 5-HT2A ligands. This project will for the first time characterise the effects of 5-HT2A agonists on both sleep and wake quantity and quality, establish novel metrics of behavioural arousal and its electrophysiological correlates in freely behaving mice in accordance with the 3Rs, and address the relationship between REM sleep and attentional performance.

大脑中的5-羟色胺能信号对广泛的功能很重要-从食欲，体温调节和睡眠到焦虑，学习和记忆。研究表明，对多巴胺能系统的操作可以影响不同警觉状态的数量和分布。例如，在人类和实验室动物中使用选择性5-羟色胺再摄取抑制剂治疗后，观察到快速眼动（REM）睡眠（使用常规标准定义）几乎完全消除。令人惊讶的是，快速眼动睡眠的丧失似乎并没有导致任何明显的负面后果。这表明快速眼动睡眠没有任何生物学功能，或者增强的多巴胺能系统导致发生改变或混合的警觉状态，可以在功能上取代真正的快速眼动睡眠。如果后者是真的，那么多巴胺能系统的一个关键作用是控制特定睡眠状态的质量，而不是数量。本项目的目的是验证5-HT 2A激动剂对自由活动小鼠皮层神经活动和行为的影响。选择这类化合物是因为我们的初步研究表明它们对小鼠的快速眼动睡眠有很强的抑制作用。在这项研究中，我们将在自由活动的小鼠的新皮层进行慢性电生理记录，结合EMG，加速度计，位置眼跟踪和瞳孔直径跨越自发觉醒和睡眠，以及在行为任务执行期间和之后的裸盖菇素和其他5-HT 2A配体的管理。该项目将首次验证5-HT 2A激动剂对睡眠和觉醒数量和质量的影响，根据3R建立自由行为小鼠的行为唤醒及其电生理相关性的新指标，并解决REM睡眠和注意力表现之间的关系。