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A competitive inhibitory circuit for selection of active and passive fear responses

机译：用于选择主动和被动恐惧反应的竞争性抑制电路

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摘要

When faced with threat, the survival of an organism is contingent upon the selection of appropriate active or passive behavioural responses(1-3). Freezing is an evolutionarily conserved passive fear response that has been used extensively to study the neuronal mechanisms of fear and fear conditioning in rodents(4). However, rodents also exhibit active responses such as flight under natural conditions(2). The central amygdala (CEA) is a forebrain structure vital for the acquisition and expression of conditioned fear responses, and the role of specific neuronal sub-populations of the CEA in freezing behaviour is well-established(1,5-7). Whether the CEA is also involved in flight behaviour, and how neuronal circuits for active and passive fear behaviour interact within the CEA, are not yet understood. Here, using in vivo optogenetics and extracellular recordings of identified cell types in a behavioural model in which mice switch between conditioned freezing and flight, we show that active and passive fear responses are mediated by distinct and mutually inhibitory CEA neurons. Cells expressing corticotropin-releasing factor (CRF+) mediate conditioned flight, and activation of somatostatin-positive (SOM+) neurons initiates passive freezing behaviour. Moreover, we find that the balance between conditioned flight and freezing behaviour is regulated by means of local inhibitory connections between CRF+ and SOM+ neurons, indicating that the selection of appropriate behavioural responses to threat is based on competitive interactions between two defined populations of inhibitory neurons, a circuit motif allowing for rapid and flexible action selection.
机译：当面临威胁时，生物体的生存取决于选择适当的主动或被动行为反应（1-3）。冷冻是一种进化保守的被动恐惧反应，已广泛用于研究啮齿动物恐惧和恐惧条件的神经元机制（4）。但是，啮齿动物在自然条件下也会表现出积极的反应，例如逃跑（2）。中央杏仁核（CEA）是对条件恐惧反应的获得和表达至关重要的前脑结构，并且CEA特定神经元亚群在冰冻行为中的作用是公认的（1,5-7）。 CEA是否也参与飞行行为，以及在CEA中主动和被动恐惧行为的神经回路如何相互作用。在这里，使用体内光遗传学和在小鼠在条件性冰冻和飞行之间切换的行为模型中确定的细胞类型的细胞外记录，我们显示了主动和被动的恐惧反应是由不同且相互抑制的CEA神经元介导的。表达促肾上腺皮质激素释放因子（CRF +）的细胞介导条件性飞行，而生长抑素阳性（SOM +）神经元的激活引发被动冻结行为。此外，我们发现条件飞行和冰冻行为之间的平衡是通过CRF +和SOM +神经元之间的局部抑制联系来调节的，这表明对威胁的适当行为反应的选择是基于两个定义的抑制神经元群体之间的竞争性相互作用，允许快速灵活选择动作的电路图案。

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  • 来源
    《Nature》 |2017年第7639期|96-100|共5页
  • 作者

    Fadok Jonathan P.; Krabbe Sabine; Markovic Milica; Courtin Julien; Xu Chun; Massi Lema; Botta Paolo; Bylund Kristine; Mueller Christian; Kovacevic Aleksandar; Tovote Philip; Luthi Andreas;

  • 作者单位

    Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland;

    Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland;

    Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland|Univ Basel, CH-4000 Basel, Switzerland;

    Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland;

    Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland;

    Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland;

    Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland|Univ Basel, CH-4000 Basel, Switzerland|Champalimaud Ctr Unknown, P-1400038 Lisbon, Portugal;

    Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland;

    Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland;

    Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland;

    Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland;

    Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland|Univ Basel, CH-4000 Basel, Switzerland;

  • 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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