Laboratory of Molecular Genetics, Rockefeller University, New York, NY, 10065, USA.
Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Mol Psychiatry. 2020 Mar;25(3):666-679. doi: 10.1038/s41380-018-0072-y. Epub 2018 Jun 6.
Feeding is a complex motivated behavior controlled by a distributed neural network that processes sensory information to generate adaptive behavioral responses. Accordingly, studies using appetitive Pavlovian conditioning confirm that environmental cues that are associated with food availability can induce feeding even in satiated subjects. However, in mice, appetitive conditioning generally requires intensive training and thus can impede molecular studies that often require large numbers of animals. To address this, we developed and validated a simple and rapid context-induced feeding (Ctx-IF) task in which cues associated with food availability can later lead to increased food consumption in sated mice. We show that the associated increase in food consumption is driven by both positive and negative reinforcement and that spaced training is more effective than massed training. Ctx-IF can be completed in ~1 week and provides an opportunity to study the molecular mechanisms and circuitry underlying non-homeostatic eating. We have used this paradigm to map brain regions that are activated during Ctx-IF with cFos immunohistochemistry and found that the insular cortex, and other regions, are activated following exposure to cues denoting the availability of food. Finally, we show that inhibition of the insular cortex using GABA agonists impairs performance of the task. Our findings provide a novel assay in mice for defining the functional neuroanatomy of appetitive conditioning and identify specific brain regions that are activated during the development of learned behaviors that impact food consumption.
摄食是一种复杂的受动机体行为，由一个分布式神经网络控制，该网络处理感官信息以产生适应性的行为反应。因此，使用有吸引力的巴甫洛夫条件反射的研究证实，与食物供应相关的环境线索即使在饱腹的实验对象中也能诱导摄食。然而，在小鼠中，有吸引力的条件反射通常需要密集的训练，因此会阻碍通常需要大量动物的分子研究。为了解决这个问题，我们开发并验证了一种简单而快速的上下文诱导摄食（Ctx-IF）任务，在该任务中，与食物供应相关的线索可以在以后导致饱腹小鼠增加食物消耗。我们表明，食物消耗的增加是由正强化和负强化驱动的，并且间隔训练比集中训练更有效。Ctx-IF 可以在大约 1 周内完成，为研究非稳态进食的分子机制和电路提供了机会。我们已经使用该范式通过 cFos 免疫组织化学来映射在 Ctx-IF 期间被激活的大脑区域，并且发现岛叶皮层和其他区域在暴露于表示食物可用性的线索后被激活。最后，我们表明使用 GABA 激动剂抑制岛叶皮层会损害任务的表现。我们的研究结果为定义有吸引力的条件反射的功能神经解剖学提供了一种新的小鼠检测方法，并确定了在学习行为发展期间被激活的特定大脑区域，这些学习行为会影响食物消耗。
