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Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala

机译：5-羟色胺参与了杏仁核的焦虑和恐惧刺激循环

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摘要

Serotonin (also known as 5-hydroxytryptamine (5-HT)) is a neurotransmitter that has an essential role in the regulation of emotion. However, the precise circuits have not yet been defined through which aversive states are orchestrated by 5-HT. Here we show that 5-HT from the dorsal raphe nucleus (5-HTDRN) enhances fear and anxiety and activates a subpopulation of corticotropin-releasing factor (CRF) neurons in the bed nucleus of the stria terminal's (CRFBNST,) in mice. Specifically, 5-HTDRN projections to the BNST, via actions at 5-HT2C receptors (5-HT(2C)Rs), engage a CRFBNST inhibitory microcircuit that silences anxiolytic BNST outputs to the ventral tegmental area and lateral hypothalamus. Furthermore, we demonstrate that this CRFBNST inhibitory circuit underlies aversive behaviour following acute exposure to selective serotonin reuptake inhibitors (SSRIs). This early aversive effect is mediated via the corticotrophin-releasing factor type 1 receptor (CRF1R, also known as CRHR1), given that CRF1R antagonism is sufficient to prevent acute SSRI-induced enhancements in aversive learning. These results reveal an essential 5-HTDRN -> CRFBNST circuit governing fear and anxiety, and provide a potential mechanistic explanation for the clinical observation of early adverse events to SSRI treatment in some patients with anxiety disorders(1,2).
机译：5-羟色胺（也称为5-羟色胺（5-HT））是一种神经递质，在调节情绪方面具有重要作用。但是，还没有定义精确的电路，通过这些电路，5-HT可以协调厌恶状态。在这里，我们显示了来自背脊核（5-HTDRN）的5-HT增强了恐惧和焦虑，并激活了小鼠纹状终末床（CRFBNST，）的床核中促肾上腺皮质激素释放因子（CRF）神经元的亚群。具体来说，通过对5-HT2C受体（5-HT（2C）Rs）的作用，5-HTDRN投射到BNST会参与CRFBNST抑制性微电路，从而使抗焦虑BNST输出到腹侧被盖区和下丘脑外侧沉默。此外，我们证明此CRFBNST抑制电路是急性暴露于选择性5-羟色胺再摄取抑制剂（SSRIs）后的厌恶行为的基础。鉴于CRF1R拮抗作用足以防止SSRI引起的急性厌恶性学习增强，这种早期的厌恶作用是通过1型促肾上腺皮质激素释放因子受体（CRF1R，也称为CRHR1）介导的。这些结果揭示了控制恐惧和焦虑的必不可少的5-HTDRN-> CRFBNST回路，并为某些焦虑症患者对SSRI治疗的早期不良事件的临床观察提供了潜在的机理解释（1,2）。

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  • 来源
    《Nature》 |2016年第7618期|97-101|共5页
  • 作者

    Marcinkiewcz Catherine A.; Mazzone Christopher M.; DAgostino Giuseppe; Halladay Lindsay R.; Hardaway J. Andrew; DiBerto Jeffrey F.; Navarro Montserrat; Burnham Nathan; Cristiano Claudia; Dorrier Cayce E.; Tipton Gregory J.; Ramakrishnan Charu; Kozicz Tamas; Deisseroth Karl; Thiele Todd E.; McElligott Zoe A.; Holmes Andrew; Heisler Lora K.; Kash Thomas L.;

  • 作者单位

    Univ North Carolina Chapel Hill, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA;

    Univ North Carolina Chapel Hill, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA|Univ North Carolina Chapel Hill, Sch Med, Curriculum Neurobiol, Chapel Hill, NC 27599 USA;

    Univ Aberdeen, Rowett Inst Nutr & Hlth, Aberdeen AB25 2ZD, Scotland;

    NIAAA, NIH, Rockville, MD 20852 USA;

    Univ North Carolina Chapel Hill, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA;

    Univ North Carolina Chapel Hill, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA;

    Univ North Carolina Chapel Hill, Coll Arts & Sci, Dept Psychol & Neurosci, Chapel Hill, NC 27599 USA;

    Univ North Carolina Chapel Hill, Coll Arts & Sci, Dept Psychol & Neurosci, Chapel Hill, NC 27599 USA;

    Univ Aberdeen, Rowett Inst Nutr & Hlth, Aberdeen AB25 2ZD, Scotland;

    Univ North Carolina Chapel Hill, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA;

    Univ North Carolina Chapel Hill, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA;

    Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA;

    Tulane Univ, Hayward Genet Ctr, New Orleans, LA 70112 USA|Radboud Univ Nijmegen, Med Ctr, Dept Anat, NL-6500 HB Nijmegen, Netherlands;

    Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA;

    Univ North Carolina Chapel Hill, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA|Univ North Carolina Chapel Hill, Coll Arts & Sci, Dept Psychol & Neurosci, Chapel Hill, NC 27599 USA;

    Univ North Carolina Chapel Hill, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA|Univ North Carolina Chapel Hill, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA;

    NIAAA, NIH, Rockville, MD 20852 USA;

    Univ Aberdeen, Rowett Inst Nutr & Hlth, Aberdeen AB25 2ZD, Scotland;

    Univ North Carolina Chapel Hill, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA|Univ North Carolina Chapel Hill, Sch Med, Curriculum Neurobiol, Chapel Hill, NC 27599 USA|Univ North Carolina Chapel Hill, Coll Arts & Sci, Dept Psychol & Neurosci, Chapel Hill, NC 27599 USA|Univ North Carolina Chapel Hill, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA;

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