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.

中文翻译：

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下丘脑表达GABA的伤害性感受态素的神经元调节AgRP神经元活性以控制进食行为

弓形棘突神经相关肽（AgRP）神经元在摄食中起着核心作用，并受到体内稳态激素和营养信号以及下丘脑神经元途径的复杂调节。进食也可能受到环境提示，感觉输入和其他行为的影响，这暗示了较高大脑区域的参与。但是，尚不清楚这种途径是否通过直接突触控制AgRP神经元活性来调节进食。在这里，我们显示了纹状体末端前核（aBNST）中表达伤害感受素的神经元向AgRP神经元直接产生了GABA能输入。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供应的增加而增加，它们的消融导致肥胖。此外，这些神经元从一系列上游大脑区域以及下丘脑核中获得传入输入。因此，通过将AgRP神经元连接到稳态和非稳态神经元输入端，aBNST GABA能敏Noceptin神经元可以充当进食行为的门户。