Reward-seeking behavior is fundamental to survival, but suppression of this behavior can be essential as well, even for rewards of high value. In humans and rodents, the medial prefrontal cortex (mPFC) has been implicated in suppressing reward seeking; however, despite vital significance in health and disease, the neural circuitry through which mPFC regulates reward seeking remains incompletely understood. Here, we show that a specific subset of superficial mPFC projections to a subfield of nucleus accumbens (NAc) neurons naturally encodes the decision to initiate or suppress reward seeking when faced with risk of punishment. A highly resolved subpopulation of these top-down projecting neurons, identified by 2-photon Ca²⁺ imaging and activity-dependent labeling to recruit the relevant neurons, was found capable of suppressing reward seeking. This natural activity-resolved mPFC-to-NAc projection displayed unique molecular-genetic and microcircuit-level features concordant with a conserved role in the regulation of reward-seeking behavior, providing cellular and anatomical identifiers of behavioral and possible therapeutic significance.

中文翻译：

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抑制奖赏寻求的自上而下神经机制的分子和电路动力学识别。

寻求奖励的行为是生存的基础，但抑制这种行为也很重要，即使是为了获得高价值的奖励。在人类和啮齿动物中，内侧前额叶皮层 (mPFC) 与抑制奖励寻求有关；然而，尽管对健康和疾病具有重要意义，但人们对 mPFC 调节奖赏寻求的神经回路仍未完全了解。在这里，我们展示了浅表 mPFC 投射到伏隔核 (NAc) 神经元子区域的特定子集自然编码了在面临惩罚风险时启动或抑制奖励寻求的决定。这些自上而下投射神经元的高度分辨亚群，由 2-光子 Ca ^2+识别成像和活动依赖性标记以招募相关神经元，被发现能够抑制奖励寻求。这种自然活动分辨的 mPFC-to-NAc 投射显示出独特的分子遗传学和微电路级特征，与奖赏行为调节中的保守作用一致，提供了行为和可能的治疗意义的细胞和解剖学标识符。