Extrahypothalamic GABAergic nociceptin-expressing neurons regulate AgRP neuron activity to control feeding behavior
Extrahypothalamic GABAergic nociceptin-expressing neurons regulate AgRP neuron activity to control feeding behavior
复制标题
DOI：
10.1172/jci130340
复制
发表时间：
2020-01-01
影响因子：
15.9
通讯作者：
Withers, Dominic J.
中科院分区：
文献类型：
--
作者：
Smith, Mark A.;Choudhury, Agharul I.;Withers, Dominic J.
弓状核刺鼠相关肽 (AgRP) 神经元在进食中发挥核心作用，并受到稳态激素和营养信号以及下丘脑神经元通路的复杂调节。进食也可能受到环境暗示、感官输入和其他行为的影响，这意味着高级大脑区域的参与。然而，这些途径是否通过直接突触控制 AgRP 神经元活动来调节进食尚不清楚。在这里，我们发现终纹前床核 (aBNST) 中表达伤害感受肽的神经元将 GABA 能直接输入到 AgRP 神经元上。我们发现这些神经元的激活抑制了 AgRP 神经元和进食。这些神经元的活动随着食物的供应而增加，而它们的消融会导致肥胖。此外，这些神经元接收来自一系列上游大脑区域以及下丘脑核团的传入输入。因此，aBNST GABA 能伤害感受肽神经元可能通过将 AgRP 神经元连接到稳态和非稳态神经元输入来充当进食行为的网关。
Arcuate nucleus agouti-related peptide (AgRP) neurons play a central role in feeding and are under complex regulation by both homeostatic hormonal and nutrient signals and hypothalamic neuronal pathways. Feeding may also be influenced by environmental cues, sensory inputs, and other behaviors, implying the involvement of higher brain regions. However, whether such pathways modulate feeding through direct synaptic control of AgRP neuron activity is unknown. Here, we show that nociceptin-expressing neurons in the anterior bed nuclei of the stria terminalis (aBNST) make direct GABAergic inputs onto AgRP neurons. We found that activation of these neurons inhibited AgRP neurons and feeding. The activity of these neurons increased upon food availability, and their ablation resulted in obesity. Furthermore, these neurons received afferent inputs from a range of upstream brain regions as well as hypothalamic nuclei. Therefore, aBNST GABAergic nociceptin neurons may act as a gateway to feeding behavior by connecting AgRP neurons to both homeostatic and nonhomeostatic neuronal inputs.