Rapid Reconfiguration of the Functional Connectome after Chemogenetic Locus Coeruleus Activation
Rapid Reconfiguration of the Functional Connectome after Chemogenetic Locus Coeruleus Activation
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DOI：
10.1101/527457
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发表时间：
2019-01
期刊：
影响因子：
16.2
通讯作者：
V. Zerbi;Amalia Floriou-Servou;M. Markicevic;Y. Vermeiren;Oliver Sturman;Mattia Privitera;Lukas M. von Ziegler;Kim David Ferrari;B. Weber;P. D. de Deyn;N. Wenderoth;J. Bohacek
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作者：
V. Zerbi;Amalia Floriou-Servou;M. Markicevic;Y. Vermeiren;Oliver Sturman;Mattia Privitera;Lukas M. von Ziegler;Kim David Ferrari;B. Weber;P. D. de Deyn;N. Wenderoth;J. Bohacek
蓝斑（LC）向整个前脑供应去甲肾上腺素（NE），调节许多基本的脑功能，并与多种神经精神疾病有关。虽然在人类中不可能选择性地操纵LC，但研究表明，强烈的LC激活可能会改变网络连接，以有利于显着性处理。为了验证这一假设，我们使用小鼠模型来研究LC刺激对大规模功能连接的影响，通过将LC的化学发生激活与静息状态fMRI相结合，我们称之为“化学连接组学”。LC激活迅速中断正在进行的行为，并强烈增加全脑的连接，在显着性和杏仁核网络的影响最深远。我们揭示了功能连接的变化和转录水平的α-1，α-2和β-1肾上腺素受体在整个大脑之间的直接相关性，以及NE营业额和功能连接之间的正相关性在选择的大脑区域。这些结果代表了响应LC激活的第一个全脑功能连接映射，并证明了受体表达，大脑状态和功能连接的大规模网络之间的因果关系。我们认为，大规模网络连接的这些变化对于在提高警惕和威胁检测的背景下优化神经处理至关重要。
The locus coeruleus (LC) supplies norepinephrine (NE) to the entire forebrain, regulates many fundamental brain functions, and is implicated in several neuropsychiatric diseases. Although selective manipulation of the LC is not possible in humans, studies have suggested that strong LC activation might shift network connectivity to favor salience processing. To test this hypothesis, we use a mouse model to study the impact of LC stimulation on large-scale functional connectivity by combining chemogenetic activation of the LC with resting-state fMRI, an approach we term “chemo-connectomics”. LC activation rapidly interrupts ongoing behavior and strongly increases brain-wide connectivity, with the most profound effects in the salience and amygdala networks. We reveal a direct correlation between functional connectivity changes and transcript levels of alpha-1, alpha-2, and beta-1 adrenoceptors across the brain, and a positive correlation between NE turnover and functional connectivity within select brain regions. These results represent the first brain-wide functional connectivity mapping in response to LC activation, and demonstrate a causal link between receptor expression, brain states and functionally connected large-scale networks at rest. We propose that these changes in large-scale network connectivity are critical for optimizing neural processing in the context of increased vigilance and threat detection.