State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, College of Future Technology, Peking University, Beijing 100871, China; Research Unit of Mitochondria in Brain Diseases, Chinese Academy of Medical Sciences, PKU-Nanjing Institute of Translational Medicine, Nanjing 211500, China.
Neuron. 2023 Sep 6;111(17):2727-2741.e7. doi: 10.1016/j.neuron.2023.05.023. Epub 2023 Jun 22.
Persistence in the face of failure helps to overcome challenges. But the ability to adjust behavior or even give up when the task is uncontrollable has advantages. How the mammalian brain switches behavior when facing uncontrollability remains an open question. We generated two mouse models of behavioral transition from action to no-action during exposure to a prolonged experience with an uncontrollable outcome. The transition was not caused by pain desensitization or muscle fatigue and was not a depression-/learned-helplessness-like behavior. Noradrenergic neurons projecting to GABAergic neurons within the orbitofrontal cortex (OFC) are key regulators of this behavior. Fiber photometry, microdialysis, mini-two-photon microscopy, and tetrode/optrode in vivo recording in freely behaving mice revealed that the reduction of norepinephrine and downregulation of alpha 1 receptor in the OFC reduced the number and activity of GABAergic neurons necessary for driving action behavior resulting in behavioral transition. These findings define a circuit governing behavioral switch in response to prolonged uncontrollability.
面对失败时的坚持有助于克服挑战。但是，当任务无法控制时，能够调整行为甚至放弃也有其优势。哺乳动物大脑在面对不可控性时如何切换行为仍然是一个悬而未决的问题。我们生成了两种小鼠模型，用于在经历长时间不可控结果的暴露期间，从动作行为到无动作行为的行为转变。这种转变不是由疼痛脱敏或肌肉疲劳引起的，也不是抑郁/习得性无助样行为。投射到眶额皮质（OFC）中 GABA 能神经元的去甲肾上腺素能神经元是这种行为的关键调节者。在自由活动的小鼠中进行光纤光度测定、微透析、微型双光子显微镜和四极管/光极管在体记录显示，OFC 中的去甲肾上腺素减少和 alpha 1 受体下调减少了驱动动作行为所必需的 GABA 能神经元的数量和活性，导致行为转变。这些发现定义了一个控制对长时间不可控性做出反应的行为转换的回路。
