臂旁核(PBN)在味觉和进食系统之间连接,也是传递遇险信息和威胁的重要枢纽。尽管PBN将投影发送到腹侧被盖区(VTA),调节动机行为的异质大脑区域,PBN到VTA连接的功能仍然难以捉摸。这里,通过在几种行为范式中使用雄性小鼠,我们发现VTA投影PBN神经元显著参与上下文恐惧,克制或轻度压力,但不是可口的喂养,内脏不适或热痛。这些结果表明,PBN到VTA的输入可能会在威胁下传递负面情绪。与这个概念一致,PBN到VTA谷氨酸能输入的光遗传学激活导致厌恶,这足以覆盖可口的喂养。此外,在一项可口的食物强化操作任务中,我们证明,在食物奖励获取过程中,PBN至VTA输入的瞬时光遗传学激活可消除工具性食物寻找行为,但避免了学习到的行动-结果关联.通过采用活动依赖的靶向方法,我们显示VTADA神经元通过PBN传入激活而脱离,暗示VTA非DA神经元可能介导PBN传入调控。我们进一步表明,通过PBN输入功能招募的VTA神经元的光遗传学激活导致厌恶,抑制可口的喂养并脱离可口的食物自我管理行为。最后,我们证明了VTA谷氨酸能的瞬时激活,但不是GABA,神经元概括了PBN输入对食物自我管理行为的负调节。一起来看,我们发现PBN到VTA的输入传递了负面影响,可能通过VTA谷氨酸能神经元脱离工具食物寻找行为。显著性声明PBN接收多个输入,因此很好地定位成路由各种模态的信息,以使不同的下游电路相应地参与或响应。我们证明了PBN到VTA的输入传达了负面影响,然后触发了自适应的优先响应,以通过扣留持续的行为来满足相关的需求,例如本研究中显示的可口食物寻找或摄入。它具有进化意义,因为准备应对紧张的情况或威胁优先于寻求促进生存的食物。了解如何产生适当的适应性反应将为各种应对行为的电路机制提供新的见解,以应对不断变化的环境刺激。
The parabrachial nucleus (PBN) interfaces between taste and feeding systems and is also an important hub for relaying distress information and threats. Despite that the PBN sends projections to the ventral tegmental area (VTA), a heterogeneous brain region that regulates motivational behaviors, the function of the PBN-to-VTA connection remains elusive. Here, by using male mice in several behavioral paradigms, we discover that VTA-projecting PBN neurons are significantly engaged in contextual fear, restraint or mild stress but not palatable feeding, visceral malaise, or thermal pain. These results suggest that the PBN-to-VTA input may relay negative emotions under threat. Consistent with this notion, optogenetic activation of PBN-to-VTA glutamatergic input results in aversion, which is sufficient to override palatable feeding. Moreover, in a palatable food-reinforced operant task, we demonstrate that transient optogenetic activation of PBN-to-VTA input during food reward retrieval disengages instrumental food-seeking behaviors but spares learned action-outcome association. By using an activity-dependent targeting approach, we show that VTA DA neurons are disengaged by the PBN afferent activation, implicating that VTA non-DA neurons may mediate PBN afferent regulation. We further show that optogenetic activation of VTA neurons functionally recruited by the PBN input results in aversion, dampens palatable feeding, and disengages palatable food self-administration behavior. Finally, we demonstrate that transient activation of VTA glutamatergic, but not GABAergic, neurons recapitulates the negative regulation of the PBN input on food self-administration behavior. Together, we reveal that the PBN-to-VTA input conveys negative affect, likely through VTA glutamatergic neurons, to disengage instrumental food-seeking behaviors.SIGNIFICANCE STATEMENT The PBN receives multiple inputs and thus is well positioned to route information of various modalities to engage different downstream circuits to attend or respond accordingly. We demonstrate that the PBN-to-VTA input conveys negative affect and then triggers adaptive prioritized responses to address pertinent needs by withholding ongoing behaviors, such as palatable food seeking or intake shown in the present study. It has evolutionary significance because preparing to cope with stressful situations or threats takes priority over food seeking to promote survival. Knowing how appropriate adaptive responses are generated will provide new insights into circuitry mechanisms of various coping behaviors to changing environmental stimuli.