Deciphering a neuronal circuit that mediates appetite.
Deciphering a neuronal circuit that mediates appetite.
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DOI：
10.1038/nature10899
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发表时间：
2012-03-14
期刊：
影响因子：
64.8
通讯作者：
Palmiter, Richard D.
中科院分区：
文献类型：
--
作者：
Wu, Qi;Clark, Michael S.;Palmiter, Richard D.
已知共表达刺豚鼠相关蛋白（AgRP）、神经肽Y（NPY）和γ-氨基丁酸（GABA）的下丘脑神经元通过整合各种营养、激素和神经元信号来促进进食和体重增加。这些神经元的消融导致进食停止，这伴随着它们投射的大多数区域中的Fos激活。先前的实验表明，随后的饥饿是由于臂旁核（PBN）的异常激活，它可以通过在关键适应期内促进PBN中的GABAA受体信号传导来防止。我们假设，从AgRP神经元到PBN的GABA能抑制的丧失导致PBN的异常激活，这反过来又抑制进食。然而，PBN兴奋性输入的来源是未知的。在这里，我们表明，在孤束核（NTS）和尾侧多巴胺能神经元的多巴胺能神经元控制PBN神经元的兴奋性和抑制进食。阻断5-HT 3受体信号在喙NTS的长期管理昂丹司琼或遗传失活的Tph 2在尾部神经元，项目的NTS保护免受饥饿时，AgRP神经元消融。此外，通过NTS对PBN中的N-甲基D-天冬氨酸（NMDA）型谷氨酸受体的谷氨酸能信号传导的遗传失活防止饥饿。我们还表明，抑制PBN的神经元放电后恢复正常的食欲AgRP神经元消融，而它促进体重增加没有AgRP神经元消融。因此，我们认为PBN是一个重要的枢纽，它整合了来自几个大脑区域的信号，以双向调节进食和体重。
Hypothalamic neurons that co-express agouti-related protein (AgRP), neuropeptide Y (NPY), and γ-amino-butyric acid (GABA) are known to promote feeding and weight gain by integration of various nutritional, hormonal, and neuronal signals. Ablation of these neurons leads to cessation of feeding that is accompanied by Fos activation in most regions where they project. Previous experiments indicate that the ensuing starvation is due to aberrant activation of the parabrachial nucleus (PBN) and it could be prevented by facilitating GABAA receptor signaling in the PBN within a critical adaptation period. We hypothesized that loss of GABAergic inhibition from AgRP neurons to the PBN leads to abnormal activation of the PBN, which in turn inhibits feeding. However, the source of the excitatory inputs to the PBN was unknown. Here we show that glutamatergic neurons in the nucleus tractus solitarius (NTS) and caudal serotonergic neurons control the excitability of PBN neurons and inhibit feeding. Blockade of 5-HT3 receptor signaling in the rostral NTS by either chronic administration of ondansetron or genetic inactivation of Tph2 in caudal serotonergic neurons that project to the NTS protects against starvation when AgRP neurons are ablated. Moreover, genetic inactivation of glutamatergic signaling by the NTS onto N-methyl D-aspartate (NMDA)-type glutamate receptors in the PBN prevents starvation. We also demonstrate that suppressing glutamatergic output of the PBN reinstates normal appetite after AgRP neuron ablation, whereas it promotes weight gain without AgRP neuron ablation. Hence, we identify the PBN as an important hub that integrates signals from several brain regions to bidirectionally modulate feeding and body weight.
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影响因子：
30.8
作者：
KAPLITT, MG;LEONE, P;DURING, MJ
通讯作者：
DURING, MJ
影响因子：
2.9
作者：
Takase, Luiz Fernando;Nogueira, Maria Ines
通讯作者：
Nogueira, Maria Ines
影响因子：
16.2
作者：
Hnasko, Thomas S.;Chuhma, Nao;Zhang, Hui;Goh, Germaine Y.;Sulzer, David;Palmiter, Richard D.;Rayport, Stephen;Edwards, Robert H.
通讯作者：
Edwards, Robert H.
5-HT3受体 - 结构与功能之间的关系。
影响因子：
4.7
作者：
Barnes NM;Hales TG;Lummis SC;Peters JA
通讯作者：
Peters JA
DOI：
10.1523/jneurosci.2449-08.2008
发表时间：
2008-09-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Wu Q;Howell MP;Palmiter RD
通讯作者：
Palmiter RD