Medial Prefrontal Cortex Neural Plasticity, Orexin Receptor 1 Signaling, and Connectivity with the Lateral Hypothalamus Are Necessary in Cue-Potentiated Feeding
Medial Prefrontal Cortex Neural Plasticity, Orexin Receptor 1 Signaling, and Connectivity with the Lateral Hypothalamus Are Necessary in Cue-Potentiated Feeding
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DOI：
10.1523/jneurosci.1803-19.2020
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发表时间：
2020-02-19
影响因子：
5.3
通讯作者：
Petrovich, Gorica D.
中科院分区：
文献类型：
--
作者：
Cole, Sindy;Keefer, Sara E.;Petrovich, Gorica D.
认知过程有助于控制摄食行为，并在支持生理需求时帮助生物体生存。它们可能会变得适应不良，例如在没有饥饿的情况下，当学习的食物线索驱动进食时。联想学习是线索驱动的食物寻求和消费的基础，巴甫洛夫线索食物条件反射的行为范式已经建立。然而，神经回路可塑性的神经机制在提示食物学习，提示记忆回忆，和随后的食物动机是未知的。在这里，我们证明了内侧前额叶皮层（mPFC）是一个网站的学习诱导的可塑性和信号的神经肽食欲素内的mPFC介导的线索强化喂养（CPF）。首先，使用神经元激活的标记物c-fos，我们证实了mPFC在CPF期间被激活。接下来，为了评估在提示食物学习和随后的CPF期间是否激活相同的mPFC神经元集合，我们在c-fos-lacZ转基因雄性和雌性大鼠中使用Daun 02化学发生失活方法。选择性失活的mPFC神经元，活跃在最后的提示食物训练会议期间废除CPF在测试中，表明mPFC是一个网站的可塑性。我们假设食物提示记忆和进食动机的整合需要mPFC与外侧下丘脑的通信，并表明该系统的断开废除CPF。然后，我们发现，外侧下丘脑食欲素产生神经元的项目mPFC。最后，我们阻断了mPFC中的食欲素受体1信号传导，并表明它是线索驱动消费所必需的神经调节剂。总之，我们的研究结果确定了一个因果函数的mPFC的认知动机吃。
Cognitive processes contribute to the control of feeding behavior and help organism's survival when they support physiological needs. They can become maladaptive, such as when learned food cues drive feeding in the absence of hunger. Associative learning is the basis for cue-driven food seeking and consumption, and behavioral paradigms with Pavlovian cue-food conditioning are well established. Yet, the neural mechanisms underlying circuit plasticity across cue-food learning, cue memory recall,and subsequent food motivation are unknown. Here, we demonstrated the medial prefrontal cortex (mPFC) is a site of learning-induced plasticity and signaling of the neuropeptide orexin within the mPFC mediates cue potentiated feeding (CPF). First, using a marker of neuronal activation, c-fos, we confirmed that the mPFC is activated during CPF. Next, to assess whether the same mPFC neuronal ensemble is activated during cue-food learning and later CPF, we used the Daun02 chemogenetic inactivation method in c-fos-lacZ transgenic male and female rats. Selective inactivation of the mPFC neurons that were active during the last cue-food training session abolished CPF during test, demonstrating that the mPFC is a site of plasticity. We postulated that integration of food cue memory and feeding motivation requires mPFC communications with lateral hypothalamus and showed that disconnection of that system abolished CPF. Then we showed that lateral hypothalamus orexin-producing neurons project to the mPFC. Finally, we blocked orexin receptor 1 signaling in the mPFC and showed that it is a neuromodulator necessary for the cue-driven consumption. Together, our findings identify a causal function for the mPFC in the cognitive motivation to eat.