Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Int J Obes (Lond). 2013 Jul;37(7):1012-9. doi: 10.1038/ijo.2012.174. Epub 2012 Oct 16.
Cues that are associated with the availability of food are known to trigger food anticipatory activity (FAA). This activity is expressed as increased locomotor activity and enables an animal to prepare for maximal utilization of nutritional resources. Although the exact neural network that mediates FAA is still unknown, several studies have revealed that the medial hypothalamus is involved. Interestingly, this area is responsive to the anorexigenic hormone leptin and the orexigenic hormone ghrelin that have been shown to modulate FAA. However, how FAA is regulated by neuronal activity and how leptin and ghrelin modulate this activity is still poorly understood.
We aimed to examine how the total neuronal population and individual neurons in the medial hypothalamus respond to cue-signaled food availability in awake, behaving rats. In addition, ghrelin and leptin were injected to investigate whether these hormones could have a modulatory role in the regulation of FAA.
Using in vivo electrophysiology, neuronal activity was recorded in the medial hypothalamus in freely moving rats kept on a random feeding schedule, in which a light cue signaled upcoming food delivery. Ghrelin and leptin were administered systemically following the behavioral paradigm.
The food-predictive cue induced FAA as well as a significant increase in neural activity on a population level. More importantly, a sub-population of medial hypothalamic neurons displayed highly correlated identical responses to both ghrelin and FAA, suggesting that these neurons are part of the network that regulates FAA.
This study reveals a role for ghrelin, but not leptin, signaling within medial hypothalamus in FAA on both a population level and in single cells, identifying a subset of neurons onto which cue information and ghrelin signaling converge, possibly to drive FAA.
已知与食物供应相关的线索会引发食物预期活动（FAA）。这种活动表现为增加的运动活动，使动物能够为最大程度地利用营养资源做好准备。尽管介导 FAA 的精确神经网络仍不清楚，但已有几项研究表明，内侧下丘脑参与其中。有趣的是，该区域对厌食激素瘦素和食欲激素 ghrelin 有反应，这两种激素已被证明可以调节 FAA。然而，FAA 如何受到神经元活动的调节，以及瘦素和 ghrelin 如何调节这种活动，仍知之甚少。
我们旨在研究在清醒、行为活跃的大鼠中，内侧下丘脑的总神经元群体和单个神经元如何对线索信号的食物供应做出反应。此外，还注射了 ghrelin 和 leptin，以研究这些激素是否可以在 FAA 的调节中发挥调节作用。
使用活体电生理学，在自由活动的大鼠的内侧下丘脑记录神经元活动，这些大鼠保持随机喂养时间表，其中光线索信号表示即将到来的食物输送。在行为范式之后，系统地给予 ghrelin 和 leptin。
食物预测线索诱导 FAA 以及神经元群体水平上的显著增加。更重要的是，内侧下丘脑的一个亚群神经元对 ghrelin 和 FAA 表现出高度相关的相同反应，表明这些神经元是调节 FAA 的网络的一部分。
这项研究揭示了 ghrelin 信号在 FAA 的群体水平和单个细胞中的作用，但 leptin 信号没有作用，确定了内侧下丘脑内的一组神经元，这些神经元接收线索信息和 ghrelin 信号的汇聚，可能驱动 FAA。
