RIKEN Brain Science Institute, Laboratory for Neural Circuitry of Memory, Wako, Japan.
Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Tokyo, Japan.
Nat Neurosci. 2017 Nov;20(11):1602-1611. doi: 10.1038/nn.4642. Epub 2017 Sep 18.
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.
去甲肾上腺素通过传统上认为在脑干蓝斑核（LC）中的同质细胞群来调节大脑的全局状态和各种行为。然而，LC 如何协调不同的行为功能尚不清楚。我们在大鼠中报告了 LC 的模块化组织，赋予了独特的神经投射模式和编码特性，以灵活指定对立的行为学习状态。LC 投射映射显示出具有特定解剖连接的功能不同的细胞模块。投射到杏仁核的集合促进了厌恶学习，而独立的投射到内侧前额叶皮层的集合则消除了对厌恶反应的抑制，从而实现了灵活的行为。LC 神经元表现出依赖于上下文的相互关系，中等程度的、离散的激活不同的细胞群可以由恐惧或安全线索引起，而强烈的厌恶刺激则可以强烈地招募大多数细胞。这些结果表明 LC 中存在模块化组织，其中组合激活模式与投射和行为特异性细胞群协调，从而能够对情绪反应和行为灵活性进行自适应调整。
