To adapt to threats in the environment, animals must predict them and engage in defensive behavior. While the representation of a prediction error signal for reward has been linked to dopamine, a neuromodulatory prediction error for aversive learning has not been identified. We measured and manipulated norepinephrine release during threat learning using optogenetics and a novel fluorescent norepinephrine sensor. We found that norepinephrine response to conditioned stimuli reflects aversive memory strength. When delays between auditory stimuli and footshock are introduced, norepinephrine acts as a prediction error signal. However, temporal difference prediction errors do not fully explain norepinephrine dynamics. To explain noradrenergic signaling, we used an updated reinforcement learning model with uncertainty about time and found that it explained norepinephrine dynamics across learning and variations in temporal and auditory task structure. Norepinephrine thus combines cognitive and affective information into a predictive signal and links time with the anticipation of danger.

中文翻译：

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额叶去甲肾上腺素代表不确定性下的威胁预测错误

为了适应环境中的威胁，动物必须预测它们并采取防御行为。虽然奖励预测误差信号的表示与多巴胺有关，但厌恶性学习的神经调节预测误差尚未确定。我们使用光遗传学和新型荧光去甲肾上腺素传感器测量和操纵威胁学习过程中去甲肾上腺素的释放。我们发现去甲肾上腺素对条件刺激的反应反映了厌恶记忆的强度。当听觉刺激和足部电击之间出现延迟时，去甲肾上腺素充当预测误差信号。然而，时间差异预测误差并不能完全解释去甲肾上腺素动力学。为了解释去甲肾上腺素信号传导，我们使用了更新的具有时间不确定性的强化学习模型，发现它解释了学习过程中去甲肾上腺素的动态以及时间和听觉任务结构的变化。因此，去甲肾上腺素将认知和情感信息结合成预测信号，并将时间与对危险的预期联系起来。