Rapid, reversible activation of AgRP neurons drives feeding behavior in mice
Rapid, reversible activation of AgRP neurons drives feeding behavior in mice
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DOI：
10.1172/jci46229
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发表时间：
2011-04-01
影响因子：
15.9
通讯作者：
Lowell, Bradford B.
中科院分区：
文献类型：
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作者：
Krashes, Michael J.;Koda, Shuichi;Lowell, Bradford B.
几个不同的神经元群体参与调节能量稳态。其中，刺鼠相关蛋白(AgRP)神经元被认为促进进食和体重增加；然而，支持这一观点的证据并不完整。使用由设计师药物独有激活的设计师受体(DREADD)技术来提供对小鼠神经元活动的特异和可逆调节，我们已经证明，AgRP神经元的急性激活迅速而戏剧性地诱导进食，减少能量消耗，并最终增加脂肪储存。撤除刺激后，上述效应均恢复到基线水平。相反，抑制饥饿小鼠的AgRP神经元活动会减少食物的摄入量。综上所述，这些发现表明，AgRP神经元的活动对于进食是必要的，也是充分的。有趣的是，激活AgRP神经元有效地增加了觅食的动机，也驱动了强烈的觅食行为，表明AgRP神经元参与了控制多个水平的摄食行为的大脑部位。由于其易用性和对急性和慢性调节的适用性，DREADD技术非常适合于研究假想的调节能量平衡的神经回路。
Several different neuronal populations are involved in regulating energy homeostasis. Among these, agouti-related protein (AgRP) neurons are thought to promote feeding and weight gain; however, the evidence supporting this view is incomplete. Using designer receptors exclusively activated by designer drugs (DREADD) technology to provide specific and reversible regulation of neuronal activity in mice, we have demonstrated that acute activation of AgRP neurons rapidly and dramatically induces feeding, reduces energy expenditure, and ultimately increases fat stores. All these effects returned to baseline after stimulation was withdrawn. In contrast, inhibiting AgRP neuronal activity in hungry mice reduced food intake. Together, these findings demonstrate that AgRP neuron activity is both necessary and sufficient for feeding. Of interest, activating AgRP neurons potently increased motivation for feeding and also drove intense food-seeking behavior, demonstrating that AgRP neurons engage brain sites controlling multiple levels of feeding behavior. Due to its ease of use and suitability for both acute and chronic regulation, DREADD technology is ideally suited for investigating the neural circuits hypothesized to regulate energy balance.