Novelty preference (NP) is an evolutionarily conserved, essential survival mechanism often dysregulated in neuropsychiatric disorders. NP is mediated by a motivational dopamine signal that increases in response to novel stimuli, thereby driving exploration. However, the mechanism by which once-novel stimuli transition to familiar stimuli is unknown. Here we describe a neuroanatomical substrate for familiarity signaling, the interpeduncular nucleus (IPN) of the midbrain, which is activated as novel stimuli become familiar with multiple exposures. In mice, optogenetic silencing of IPN neurons increases salience of and interaction with familiar stimuli without affecting novelty responses, whereas photoactivation of the same neurons reduces exploration of novel stimuli mimicking familiarity. Bidirectional control of NP by the IPN depends on familiarity signals and novelty signals arising from excitatory habenula and dopaminergic ventral tegmentum inputs, which activate and reduce IPN activity, respectively. These results demonstrate that familiarity signals through unique IPN circuitry that opposes novelty seeking to control NP.

中文翻译：

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熟悉信令和新颖性偏好基础的基于电路的机制

新奇偏好（NP）是一种在神经精神疾病中常常失调的进化保守的基本生存机制。NP由多巴胺激发信号介导，该信号响应新的刺激而增加，从而推动了探索。但是，从新的刺激转变为熟悉的刺激的机制尚不清楚。在这里，我们描述了一个神经解剖学底物，用于熟悉信号传导，中脑的椎间盘核（IPN），随着新的刺激物与多次接触而被激活。在小鼠中，IPN神经元的光遗传沉默可提高熟悉刺激的显着性并与之互动，而不会影响新奇反应，而同一神经元的光激活则可减少模仿熟悉性的新刺激的探索。IPN对NP的双向控制取决于兴奋性哈贝拉和多巴胺能腹盖膜输入所产生的熟悉度信号和新颖性信号，它们分别激活和降低IPN活性。这些结果表明，熟悉程度是通过独特的IPN电路发出的，该电路与寻求控制NP的新颖性相反。