蓝斑锚定了一个三突触回路，控制着恐惧引起的摄食抑制。
Locus coeruleus anchors a trisynaptic circuit controlling fear-induced suppression of feeding.
机构信息
Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
出版信息
Neuron. 2021 Mar 3;109(5):823-838.e6. doi: 10.1016/j.neuron.2020.12.023. Epub 2021 Jan 20.
Abstract
The circuit mechanisms underlying fear-induced suppression of feeding are poorly understood. To help fill this gap, mice were fear conditioned, and the resulting changes in synaptic connectivity among the locus coeruleus (LC), the parabrachial nucleus (PBN), and the central nucleus of amygdala (CeA)-all of which are implicated in fear and feeding-were studied. LC neurons co-released noradrenaline and glutamate to excite PBN neurons and suppress feeding. LC neurons also suppressed inhibitory input to PBN neurons by inducing heterosynaptic, endocannabinoid-dependent, long-term depression of CeA synapses. Blocking or knocking down endocannabinoid receptors in CeA neurons prevented fear-induced depression of CeA synaptic transmission and fear-induced suppression of feeding. Altogether, these studies demonstrate that LC neurons play a pivotal role in modulating the circuitry that underlies fear-induced suppression of feeding, pointing to new ways of alleviating stress-induced eating disorders.
摘要
恐惧抑制进食的电路机制尚不清楚。为了填补这一空白，对恐惧条件的小鼠进行了研究，研究了蓝斑核（LC）、臂旁核（PBN）和杏仁中央核（CeA）之间的突触连接变化，这些核都与恐惧和进食有关。LC 神经元共同释放去甲肾上腺素和谷氨酸来兴奋 PBN 神经元并抑制进食。LC 神经元还通过诱导 CeA 突触的异突触、内源性大麻素依赖性、长时程抑制来抑制对 PBN 神经元的抑制性输入。阻断或敲低 CeA 神经元中的内源性大麻素受体可防止恐惧引起的 CeA 突触传递抑制和恐惧引起的进食抑制。总之，这些研究表明 LC 神经元在调节恐惧抑制进食的电路中发挥着关键作用，为缓解应激诱导的进食障碍提供了新的方法。
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1
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Proc Natl Acad Sci U S A. 2020 Apr 14;117(15):8611-8615. doi: 10.1073/pnas.1909340117. Epub 2020 Mar 30.
2
Endocannabinoid Signaling Collapse Mediates Stress-Induced Amygdalo-Cortical Strengthening.内源性大麻素信号崩溃介导应激诱导的杏仁核-皮层强化。
Neuron. 2020 Mar 18;105(6):1062-1076.e6. doi: 10.1016/j.neuron.2019.12.024. Epub 2020 Jan 13.
3
Amygdala NPY Circuits Promote the Development of Accelerated Obesity under Chronic Stress Conditions.杏仁核 NPY 回路促进慢性应激条件下肥胖的加速发展。
Cell Metab. 2019 Jul 2;30(1):111-128.e6. doi: 10.1016/j.cmet.2019.04.001. Epub 2019 Apr 25.
4
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5
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Nat Neurosci. 2018 Sep;21(9):1260-1271. doi: 10.1038/s41593-018-0203-4. Epub 2018 Aug 13.
6
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Trends Neurosci. 2018 May;41(5):280-293. doi: 10.1016/j.tins.2018.03.007.
7
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8
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9
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Neuron. 2017 Mar 22;93(6):1464-1479.e5. doi: 10.1016/j.neuron.2017.02.034.
10
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Behav Brain Res. 2017 May 1;324:87-95. doi: 10.1016/j.bbr.2017.02.021. Epub 2017 Feb 14.
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