Genetic identification of a neural circuit that suppresses appetite.
Genetic identification of a neural circuit that suppresses appetite.
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食欲抑制发生在饭后，也发生在不宜进食的情况下，如生病或接触毒素。臂旁核（PBN）是脑干中小脑上级脚周围的一个异质神经元群，被认为在食欲抑制中起作用。PBN被认为介导由厌食激素胰淀素和胆囊收缩素以及氯化锂和脂多糖（分别模拟有毒食物和细菌感染的作用的化合物）诱导的食欲抑制。PBN的过度活跃也被认为是在成年小鼠中引起食欲相关肽（AgRP）神经元消融后引起饥饿的原因。然而，PBN神经元的身份，调节喂养是未知的，因为是功能相关的下游预测。在这里，我们确定降钙素基因相关肽（CGRP）表达神经元的PBN的外部外侧亚部，项目的杏仁核中央核（CeAlc）的侧囊分裂形成一个功能上重要的电路抑制食欲。使用遗传编码的解剖学、光遗传学和药物遗传学工具，我们证明了投射到CeAlc的PBelo CGRP神经元的激活抑制食欲。相比之下，这些神经元的抑制在小鼠通常不进食的情况下增加食物摄入，并防止成年AgRP神经元消融小鼠的饥饿。总之，我们的数据表明，从PBN到CeAlc的神经回路在不适宜进食的条件下介导食欲抑制。这种神经回路可以为治疗干预提供目标，以克服或促进食欲。
Appetite suppression occurs following a meal and also during conditions when it is unfavorable to eat, such as during illness or exposure to toxins. A brain region hypothesized to play a role in appetite suppression is the parabrachial nucleus (PBN), a heterogeneous population of neurons surrounding the superior cerebellar peduncle in the brainstem. The PBN is thought to mediate the suppression of appetite induced by the anorectic hormones amylin and cholecystokinin, as well as lithium chloride and lipopolysaccharide, compounds that mimic the effects of toxic foods and bacterial infections, respectively. Hyperactivity of the PBN is also thought to cause starvation following ablation of orexigenic agouti-related peptide (AgRP) neurons in adult mice. However, the identities of PBN neurons that regulate feeding are unknown, as are the functionally relevant downstream projections. Here we identify calcitonin gene-related peptide (CGRP)-expressing neurons in the outer external lateral subdivision of the PBN that project to the laterocapsular division of the central nucleus of the amygdala (CeAlc) as forming a functionally important circuit for the suppression of appetite. Using genetically-encoded anatomical, optogenetic, and pharmacogenetic tools, we demonstrate that activation of PBelo CGRP neurons projecting to the CeAlc suppresses appetite. In contrast, inhibition of these neurons increases food intake in circumstances when mice do not normally eat and prevents starvation in adult AgRP neuron-ablated mice. Taken together, our data demonstrate that this neural circuit from the PBN to CeAlc mediates appetite suppression in conditions when it is unfavorable to eat. This neural circuit may provide targets for therapeutic intervention to overcome or promote appetite.
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DOI：
10.1073/pnas.0700293104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Armbruster, Blaine N.;Li, Xiang;Roth, Bryan L.
通讯作者：
Roth, Bryan L.
影响因子：
2.5
作者：
Elmquist, JK;Coppari, R;Lowell, BB
通讯作者：
Lowell, BB
影响因子：
2.9
作者：
Geerling, Joel C.;Stein, Matthew K.;Loewy, Arthur D.
通讯作者：
Loewy, Arthur D.
影响因子：
1.8
作者：
Lenth, RV
通讯作者：
Lenth, RV
影响因子：
2.5
作者：
Rosen, Andrew M.;Victor, Jonathan D.;Di Lorenzo, Patricia M.
通讯作者：
Di Lorenzo, Patricia M.