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The paraventricular thalamus controls a central amygdala fear circuit

机译：脑室旁丘脑控制中央杏仁核恐惧回路

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摘要

Appropriate responses to an imminent threat brace us for adversities. The ability to sense and predict threatening or stressful events is essential for such adaptive behaviour. In the mammalian brain, one putative stress sensor is the paraventricular nucleus of the thalamus (PVT), an area that is readily activated by both physical and psychological stressors. However, the role of the PVT in the establishment of adaptive behavioural responses remains unclear. Here we show in mice that the PVT regulates fear processing in the lateral division of the central amygdala (CeL), a structure that orchestrates fear learning and expression. Selective inactivation of CeL-projecting PVT neurons prevented fear conditioning, an effect that can be accounted for by an impairment in fear-conditioning-induced synaptic potentiation onto somatostatin-expressing (SOM~+) CeL neurons, which has previously been shown to store fear memory6. Consistently, we found that PVT neurons preferentially innervate SOM~+ neurons in the CeL, and stimulation of PVT afferents facilitated SOM~+ neuron activity and promoted intra-CeL inhibition, two processes that are critical for fear learning and expression. Notably, PVT modulation of SOM~+ CeL neurons was mediated by activation of the brain-derived neurotrophic factor (BDNF) receptor tropomysin-related kinase B (TrkB). As a result, selective deletion of either Bdnfin the PVT or Trkb in SOM~+ CeL neurons impaired fear conditioning, while infusion of BDNF into the CeL enhanced fear learning and elicited unconditioned fear responses. Our results demonstrate that the PVT-CeL pathway constitutes a novel circuit essential for both the establishment of fear memory and the expression of fear responses, and uncover mechanisms linking stress detection in PVT with the emergence of adaptive behaviour.
机译：对迫在眉睫的威胁采取适当的应对措施使我们为逆境做好准备。感知和预测威胁性事件或压力事件的能力对于这种自适应行为至关重要。在哺乳动物的大脑中，一个假定的压力传感器是丘脑的脑室旁核（PVT），该区域很容易被生理和心理压力源激活。但是，PVT在建立适应性行为反应中的作用尚不清楚。在这里，我们在小鼠中发现PVT调节中央杏仁核（CeL）侧向分裂中的恐惧过程，该结构可协调恐惧的学习和表达。 CeL投射的PVT神经元的选择性失活阻止了恐惧的调节，这可以由恐惧调节诱导的表达生长激素抑制素（SOM〜+）的CeL神经元的突触增强受损来解释，以前已经证明它可以存储恐惧记忆6。一致地，我们发现PVT神经元优先支配CeL中的SOM〜+神经元，刺激PVT传入神经促进SOM〜+神经元活性并促进CeL内抑制，这两个过程对于恐惧学习和表达至关重要。值得注意的是，SOM〜+ CeL神经元的PVT​​调节是通过激活脑源性神经营养因子（BDNF）受体原肌球蛋白相关激酶B（TrkB）介导的。结果，选择性删除SOM〜+ CeL神经元中的Bdnfin PVT或Trkb会削弱恐惧条件，而将BDNF注入CeL会增强恐惧学习并引发无条件的恐惧反应。我们的结果表明，PVT-CeL途径构成了建立恐惧记忆和表达恐惧反应所必需的新型电路，并且揭示了将PVT中的压力检测与适应行为的出现联系起来的机制。

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  • 来源
    《Nature》 |2015年第7544期|455-459|共5页
  • 作者

    Mario A. Penzo; Vincent Robert; Jason Tucciarone; Dimitri De Bundel; inghui Wang; Linda Van Aelst; Martin Darvas; Luis F. Parada; Richard D. Palmiter; Miao He; Z. Josh Huang; Bo Li;

  • 作者单位

    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;

    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA,Ecole Normale Superieure de Cachan, 94230 Cachan, France;

    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA,Medical Scientist Training Program & Program in Neuroscience, Stony Brook University, Stony Brook, New York 11790, USA;

    CNRS, UMR-5203, INSERM U661, Institut de Genomique Fonctionnelle, 34090 Montpellier, France,Cnter for Neurosciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium;

    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;

    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;

    Department of Pathology,University of Washington, Seattle, Washington 98104, USA;

    Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;

    Howard Hughes Medical Institute Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA;

    Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China;

    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;

    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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