It is well known that neuropeptides have a key role in regulating feeding behaviour. However, many aspects of the mechanisms behind neuropeptide control of satiety and hunger are unclear. A recent study in mice demonstrates that two neuropeptides, neuropeptide Y and αMSH, exert opposing effects on cAMP signalling in MC4R-expressing neurons in the paraventricular nucleus of the hypothalamus (PVH^MC4R neurons), which promote satiety when stimulated. The results show how a drop in the levels of neuropeptide Y and a rise in the levels of αMSH gradually promote satiety over the course of a meal.

The researchers followed up by performing in vivo imaging that showed how cAMP signalling in PVH^MC4R neurons occurs in response to neuropeptide Y and αMSH. To do this, they virally expressed a fluorescent cAMP sensor in PVH^MC4R neurons in transgenic mice, and then imaged the neurons via two-photon microscopy through a gradient index lens. Compared with fed transgenic mice, fasted transgenic mice showed a considerable decrease in the PVH^MC4R neuron levels of cAMP. To mimic the rise in αMSH that occurs during feeding, the scientists performed optogenetic stimulation of POMC neurons, which release αMSH when activated, in transgenic mice. In response to this increase in αMSH, levels of cAMP rose considerably in PVH^MC4R neurons. Conversely, when the researchers mimicked the neuropeptide signalling associated with hunger by optogenetically stimulating AgRP neurons, which release neuropeptide Y when activated, levels of cAMP dropped.

众所周知，神经肽在调节摄食行为方面起着关键作用。然而，神经肽控制饱腹感和饥饿感背后的机制的许多方面尚不清楚。最近一项小鼠研究表明，神经肽 Y 和 αMSH 这两种神经肽对下丘脑室旁核中表达 MC4R 的神经元（PVH^MC4R 神经元）的 cAMP 信号传导产生相反的影响，受到刺激时可促进饱腹感。结果显示，神经肽 Y 水平的下降和 αMSH 水平的升高如何在进餐过程中逐渐促进饱腹感。

研究人员随后进行了体内成像，显示了 PVH^MC4R 神经元中的 cAMP 信号如何响应神经肽 Y 和 αMSH 而发生。为此，他们在转基因小鼠的 PVH^MC4R 神经元中病毒表达荧光 cAMP 传感器，然后通过梯度指数透镜通过双光子显微镜对神经元进行成像。与饲喂的转基因小鼠相比，空腹转基因小鼠的 cAMP PVH^MC4R 神经元水平显著降低。为了模拟进食过程中 αMSH 的升高，科学家们对转基因小鼠的 POMC 神经元进行了光遗传学刺激，这些神经元在激活时会释放 αMSH。作为对 αMSH 增加的响应，PVH^MC4R 神经元中的 cAMP 水平显着升高。相反，当研究人员通过光遗传学刺激 AgRP 神经元来模拟与饥饿相关的神经肽信号时，AgRP 神经元在激活时释放神经肽 Y，cAMP 水平下降。