Pontine control of rapid eye movement sleep and fear memory.
Pontine control of rapid eye movement sleep and fear memory.
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DOI：
10.1111/cns.14123
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发表时间：
2023-06
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
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在快速眼动睡眠(REM)期间，我们经常梦见强烈的非理性和负性情绪内容，并伴有姿势肌肉麻痹，但REM睡眠是如何产生的，其功能尚不清楚。在这项研究中，我们研究了脑桥背外侧被盖下核(SLD)是否是快速眼动睡眠的必要条件和充分条件，以及快速眼动睡眠消除是否改变了恐惧记忆。为了研究SLD神经元的激活是否足以诱导REM睡眠，我们通过双侧注射AAV1-hSyn-ChR2-YFP在SLD神经元中表达了通道视紫红质-2(ChR2)。接下来，我们选择性地消融了小鼠SLD中的谷氨酸或GABA能神经元，以确定对REM睡眠至关重要的神经元亚群。最后，我们利用SLD完全损毁的大鼠模型，研究了REM睡眠在巩固恐惧记忆中的作用。我们通过证明转导ChR2的SLD神经元的光激活选择性地促进大鼠从非REM(NREM)睡眠到REM睡眠的转变，证明了SLD对于REM睡眠的充分性。白喉毒素-A(DTA)致大鼠SLD损伤或特异性缺失SLD谷氨酸能神经元而不是GABA能神经元可完全消除REM睡眠，证明SLD谷氨酸能神经元对REM睡眠是必要的。然后，我们表明，在至少9个 月的时间里，通过SLD损伤消除大鼠的快速眼动睡眠，可以显著增强上下文和线索恐惧记忆的巩固，分别提高2.5%和1.0%。相反，恐惧条件作用和恐惧记忆在接下来的夜晚触发双倍的REM睡眠，而投射到内侧隔区(MS)的SLD神经元的化学激活选择性地增强了REM睡眠中的海马theta活动；这种在恐惧获得后立即进行的刺激分别将情境和线索恐惧记忆的巩固减少了60%和30%。SLD谷氨酸能神经元产生REM睡眠和REM睡眠，SLD通过海马体产生，特别是下调情境恐惧记忆。桥脑背外侧亚核(SLD)是快速眼动(REM)睡眠的必要条件和充分条件，而REM睡眠下调恐惧记忆。
We often experience dreams of strong irrational and negative emotional contents with postural muscle paralysis during rapid eye movement (REM) sleep, but how REM sleep is generated and its function remain unclear. In this study, we investigate whether the dorsal pontine sub‐laterodorsal tegmental nucleus (SLD) is necessary and sufficient for REM sleep and whether REM sleep elimination alters fear memory. To investigate whether activation of SLD neurons is sufficient for REM sleep induction, we expressed channelrhodopsin‐2 (ChR2) in SLD neurons by bilaterally injecting AAV1‐hSyn‐ChR2‐YFP in rats. We next selectively ablated either glutamatergic or GABAergic neurons from the SLD in mice in order to identify the neuronal subset crucial for REM sleep. We finally investigated the role of REM sleep in consolidation of fear memory using rat model with complete SLD lesions. We demonstrate the sufficiency of the SLD for REM sleep by showing that photo‐activation of ChR2 transfected SLD neurons selectively promotes transitions from non‐REM (NREM) sleep to REM sleep in rats. Diphtheria toxin‐A (DTA) induced lesions of the SLD in rats or specific deletion of SLD glutamatergic neurons but not GABAergic neurons in mice completely abolish REM sleep, demonstrating the necessity of SLD glutamatergic neurons for REM sleep. We then show that REM sleep elimination by SLD lesions in rats significantly enhances contextual and cued fear memory consolidation by 2.5 and 1.0 folds, respectively, for at least 9 months. Conversely, fear conditioning and fear memory trigger doubled amounts of REM sleep in the following night, and chemo‐activation of SLD neurons projecting to the medial septum (MS) selectively enhances hippocampal theta activity in REM sleep; this stimulation immediately after fear acquisition reduces contextual and cued fear memory consolidation by 60% and 30%, respectively. SLD glutamatergic neurons generate REM sleep and REM sleep and SLD via the hippocampus particularly down‐regulate contextual fear memory. Pontine sub‐laterodorsal tegmental nucleus (SLD) is necessary and sufficient for rapid‐eye‐movement (REM) sleep, and REM sleep down‐regulates fear memory.
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DOI：
10.1523/jneurosci.5525-12.2013
发表时间：
2013-03-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Datta S;O'Malley MW
通讯作者：
O'Malley MW
影响因子：
3.5
作者：
Knox D;Keller SM
通讯作者：
Keller SM
影响因子：
4.4
作者：
Arthaud, Sebastien;Varin, Christophe;Peyron, Christelle
通讯作者：
Peyron, Christelle
影响因子：
10.6
作者：
Burghardt, NS;Sullivan, GM;LeDoux, JE
通讯作者：
LeDoux, JE
影响因子：
2.9
作者：
Hunter, Amy Silvestri
通讯作者：
Hunter, Amy Silvestri