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通过光遗传调节蓝斑神经元来调节觉醒。

Tuning arousal with optogenetic modulation of locus coeruleus neurons.

机构信息

Neurosciences Program, Stanford University, Stanford, California, USA.

出版信息

Nat Neurosci. 2010 Dec;13(12):1526-33. doi: 10.1038/nn.2682. Epub 2010 Oct 31.


DOI:10.1038/nn.2682
PMID:21037585
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3174240/
Abstract

Neural activity in the noradrenergic locus coeruleus correlates with periods of wakefulness and arousal. However, it is unclear whether tonic or phasic activity in these neurons is necessary or sufficient to induce transitions between behavioral states and to promote long-term arousal. Using optogenetic tools in mice, we found that there is a frequency-dependent, causal relationship among locus coeruleus firing, cortical activity, sleep-to-wake transitions and general locomotor arousal. We also found that sustained, high-frequency stimulation of the locus coeruleus at frequencies of 5 Hz and above caused reversible behavioral arrests. These results suggest that the locus coeruleus is finely tuned to regulate organismal arousal and that bursts of noradrenergic overexcitation cause behavioral attacks that resemble those seen in people with neuropsychiatric disorders.

摘要

蓝斑核中的神经活动与觉醒和觉醒期有关。然而,尚不清楚这些神经元的紧张性或相位活动是诱导行为状态转变和促进长期觉醒所必需还是充分的。我们在小鼠中使用光遗传学工具发现,蓝斑核放电、皮层活动、睡眠到觉醒转变和一般运动唤醒之间存在频率依赖性因果关系。我们还发现,以 5 Hz 及以上的频率持续高频刺激蓝斑核会导致可逆的行为性发作。这些结果表明,蓝斑核被精细地调节以调节机体的觉醒,而去甲肾上腺素的爆发性过度兴奋会引起类似于神经精神障碍患者的行为发作。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e1/3174240/0377fe9be570/nihms-242693-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e1/3174240/21cf8333962d/nihms-242693-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e1/3174240/b252e34b3679/nihms-242693-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e1/3174240/184c98a3e770/nihms-242693-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e1/3174240/f84e7441bebc/nihms-242693-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e1/3174240/0377fe9be570/nihms-242693-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e1/3174240/21cf8333962d/nihms-242693-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e1/3174240/b252e34b3679/nihms-242693-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e1/3174240/184c98a3e770/nihms-242693-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e1/3174240/f84e7441bebc/nihms-242693-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e1/3174240/0377fe9be570/nihms-242693-f0005.jpg

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本文引用的文献

[1]
A comprehensive analysis of the effect of DSP4 on the locus coeruleus noradrenergic system in the rat.

Neuroscience. 2010-1-4

[2]
Discharge profiles of identified GABAergic in comparison to cholinergic and putative glutamatergic basal forebrain neurons across the sleep-wake cycle.

J Neurosci. 2009-9-23

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J Neurosci. 2009-9-2

[4]
Loss of GABAergic signaling by AgRP neurons to the parabrachial nucleus leads to starvation.

Cell. 2009-6-26

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Stress signalling pathways that impair prefrontal cortex structure and function.

Nat Rev Neurosci. 2009-6

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Nature. 2009-6-4

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Science. 2009-5-22

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J Neurosci. 2009-4-8

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The locus coeruleus and noradrenergic modulation of cognition.

Nat Rev Neurosci. 2009-3

[10]
A consensus definition of cataplexy in mouse models of narcolepsy.

Sleep. 2009-1

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