Modular organization of the brainstem noradrenaline system coordinates opposing learning states
Modular organization of the brainstem noradrenaline system coordinates opposing learning states
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DOI：
10.1038/nn.4642
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发表时间：
2017-11-01
影响因子：
25
通讯作者：
Johansen, Joshua P.
中科院分区：
文献类型：
--
作者：
Uematsu, Akira;Tan, Bao Zhen;Johansen, Joshua P.
去甲肾上腺素通过脑干蓝斑（LC）中传统上被认为是同质的细胞群来调节全球大脑状态和各种行为。然而，目前还不清楚LC如何协调不同的行为功能。我们报告了大鼠中的模块化LC组织，具有不同的神经投射模式和编码特性，可以灵活地指定相反的行为学习状态。LC投影映射显示具有特定解剖连接的功能不同的细胞模块。杏仁核投射合奏促进厌恶学习，而一个独立的内侧前额叶皮质投射合奏熄灭厌恶反应，使灵活的行为。LC神经元显示上下文依赖的相互关系，适度的，离散的激活不同的细胞群体的恐惧或安全的线索和强大的，全球招聘的大多数细胞强烈的厌恶刺激。这些结果表明LC中的模块化组织，其中组合激活模式与投射和行为特异性细胞群协调，从而实现情绪反应和行为灵活性的自适应调节。
Noradrenaline modulates global brain states and diverse behaviors through what is traditionally believed to be a homogeneous cell population in the brainstem locus coeruleus (LC). However, it is unclear how LC coordinates disparate behavioral functions. We report a modular LC organization in rats, endowed with distinct neural projection patterns and coding properties for flexible specification of opposing behavioral learning states. LC projection mapping revealed functionally distinct cell modules with specific anatomical connectivity. An amygdala-projecting ensemble promoted aversive learning, while an independent medial prefrontal cortex-projecting ensemble extinguished aversive responses to enable flexible behavior. LC neurons displayed context-dependent inter-relationships, with moderate, discrete activation of distinct cell populations by fear or safety cues and robust, global recruitment of most cells by strong aversive stimuli. These results demonstrate a modular organization in LC in which combinatorial activation modes are coordinated with projection-and behavior-specific cell populations, enabling adaptive tuning of emotional responding and behavioral flexibility.