Brainstem cholinergic modulation of the thalamocortical activity in urethane anesthetized mice

Brainstem cholinergic modulation of the thalamocortical activity in urethane anesthetized mice
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乌拉坦麻醉小鼠丘脑皮质活动的脑干胆碱能调节

DOI:
10.1101/2021.05.12.443746
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发表时间:
2021
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Hay Y
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在哺乳动物中,睡眠包括两个主要阶段的重复,即快速眼动(REM)睡眠和慢波睡眠(SWS)。睡眠节律的完整表达需要一个完整的丘脑皮层回路,以及它被神经调质如乙酰胆碱所调节。在REM睡眠期间观察到高音调的乙酰胆碱,而低音调的乙酰胆碱在SWS期间调制皮层慢波。脑干胆碱能神经元活动与皮质睡眠阶段相关,但这些神经元并不直接投射到皮质。相反,它们可以通过丘脑中继,特别是通过中线丘脑核,促进皮质记录的睡眠阶段调节。专注于脑干LDTg胆碱能神经元,我研究了中线丘脑单单位活动和皮质睡眠样阶段的调制过程中光遗传诱导的激活或沉默的LDTg胆碱能神经元在氨基甲酸乙酯麻醉小鼠。丘脑神经元在REM样阶段比SWS样阶段更活跃。类SWS期以爆发性放电为主,类REM期以紧张性放电为主。脑干LDTg胆碱能神经元的光遗传沉默废除REM样阶段和丘脑神经元的紧张性尖峰减少。此外,在SWS样,沉默的下状态延长和丘脑紧张性尖峰在上状态减少。刺激脑干LDTg胆碱能神经元有轻微的影响,丘脑活动,即使紧张性放电增加。令人惊讶的是,光遗传学刺激可能通过代偿机制也消除了REM样阶段。
In mammals, sleep consists in the recurrence of two main stages the rapid eye movement (REM) sleep and the slow wave sleep (SWS). The full expression of sleep rhythms requires an intact thalamocortical loop, and its modulation by neuromodulators such as acetylcholine. A high tone of acetylcholine is observed during REM sleep while a low tone of acetylcholine modulates the cortical slow waves during SWS. Brainstem Cholinergic neurons activity correlates with cortical sleep stages but these neurons do not project directly to the cortex. Instead, they could contribute to cortically-recorded sleep stage modulation via a thalamic relay, in particular via the midline thalamic nuclei. Focusing on the brainstem LDTg cholinergic neurons, I investigated how midline thalamic single unit activity and cortical sleep-like stages are modulated during optogenetic-induced activation or silencing of LDTg cholinergic neurons in urethane anesthetized mice. Thalamic neurons were more active during REM-like than SWS-like stages. Bursting activity predominated during SWS-like while tonic firing was prominent during REM-like stage. Optogenetic silencing of the brainstem LDTg cholinergic neurons abolished REM-like stages and reduced tonic spiking of thalamic neurons. Moreover, during SWS-like, silent Down states were prolonged and thalamic tonic spiking during Up states was reduced. Stimulation of the brainstem LDTg cholinergic neurons had a mild effect on thalamic activity even though tonic discharge was increased. Surprisingly, optogenetic stimulation abolished as well REM-like stages maybe through compensatory mechanisms.
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