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Nat Neurosci. 2017 Nov;20(11):1602-1611. doi: 10.1038/nn.4642. Epub 2017 Sep 18.

Modular organization of the brainstem noradrenaline system coordinates opposing learning states.

Author information

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.
Institut de Génétique Moléculaire de Montpellier, Montpellier, France.
Princeton Neuroscience Institute and Department of Psychology, Princeton, New Jersey, USA.
Bioengineering Department, Stanford University, Stanford, California, USA.
CNC Program, Stanford University, Stanford, California, USA.
Howard Hughes Medical Institute, Stanford University, Stanford, California, USA.
RIKEN BSI-Kao Collaboration Center, Wako, Japan.


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.

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