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A Fear Memory Engram and Its Plasticity in the Hypothalamic Oxytocin System

机译：下丘脑催产素系统中的恐惧记忆力及其可塑性

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摘要

Oxytocin (OT) release by axonal terminals onto the central nucleus of the amygdala exerts anxiolysis. To investigate which subpopulation of OT neurons contributes to this effect, we developed a novel method: virus-delivered genetic activity-induced tagging of cell ensembles (vGATE). With the vGATE method, we identified and permanently tagged a small subpopulation of OT cells, which, by optogenetic stimulation, strongly attenuated contextual fear-induced freezing, and pharmacogenetic silencing of tagged OT neurons impaired context-specific fear extinction, demonstrating that the tagged OT neurons are sufficient and necessary, respectively, to control contextual fear. Intriguingly, OT cell terminals of fear-experienced rats displayed enhanced glutamate release in the amygdala. Furthermore, rats exposed to another round of fear conditioning displayed 5-fold more activated magnocellular OT neurons in a novel environment than a familiar one, possibly for a generalized fear response. Thus, our results provide first evidence that hypothalamic OT neurons represent a fear memory engram.
机译：催产素（OT）通过轴突末端释放到杏仁核的中央核上施加焦炭溶解。为了探讨OT神经元的哪些亚群有助于这种效果，我们开发了一种新的方法：病毒交付的遗传活动诱导的细胞系列（VGATE）的标记。通过VGATE方法，我们鉴定并永久地标记了OT细胞的小亚群，其通过致敏刺激，强烈衰减的上下文恐惧诱导的冻结，而标记的OT神经元的药物发生沉默受损的上下文特异性恐惧灭绝，表明标记的OT神经元分别是足够的，必要的，以控制语境恐惧。有趣的是，恐惧经历的大鼠的OT细胞终端显示在杏仁醛中的增强谷氨酸释放。此外，暴露于另一轮恐惧调节的大鼠在新的环境中显示出5倍的最活化的玉米粒细胞，而不是熟悉的一种，可能是广义恐惧反应。因此，我们的结果提供了第一种证据表明，下丘脑OT神经元代表恐惧记忆engram。

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  • 来源
    《Neuron》 |2019年第1期|共22页
  • 作者

    Hasan Mazahir T.; Althammer Ferdinand; da Gouveia Miriam Silva; Goyon Stephanie; Eliava Marina; Lefevre Arthur; Kerspern Damien; Schimmer Jonas; Raftogianni Androniki; Wahis Jerome; Knobloch-Bollmann H. Sophie; Tang Yan; Liu Xinying; Jain Apar; Chavant Virginie; Goumon Yannick; Weislogel Jan-Marek; Hurlemann Rene Prime; Herpertz Sabine C.; Pitzer Claudia; Darbon Pascal; Dogbevia Godwin K.; Bertocchi Ilaria; Larkum Matthew E.; Sprengel Rolf; Bading Hilmar; Charlet Alexandre; Grinevich Valery;

  • 作者单位

    Univ Basque Country Achucarro Basque Ctr Neurosci Lab Memory Circuits Sci Pk Sede Bldg Leioa;

    German Canc Res Ctr Schaller Res Grp Neuropeptides Neuenheimer Feld 307 D-69120 Heidelberg;

    German Canc Res Ctr Schaller Res Grp Neuropeptides Neuenheimer Feld 307 D-69120 Heidelberg;

    CNRS 8 Allee Gen Rouvillois F-67000 Strasbourg France;

    German Canc Res Ctr Schaller Res Grp Neuropeptides Neuenheimer Feld 307 D-69120 Heidelberg;

    German Canc Res Ctr Schaller Res Grp Neuropeptides Neuenheimer Feld 307 D-69120 Heidelberg;

    CNRS 8 Allee Gen Rouvillois F-67000 Strasbourg France;

    German Canc Res Ctr Schaller Res Grp Neuropeptides Neuenheimer Feld 307 D-69120 Heidelberg;

    German Canc Res Ctr Schaller Res Grp Neuropeptides Neuenheimer Feld 307 D-69120 Heidelberg;

    CNRS 8 Allee Gen Rouvillois F-67000 Strasbourg France;

    German Canc Res Ctr Schaller Res Grp Neuropeptides Neuenheimer Feld 307 D-69120 Heidelberg;

    German Canc Res Ctr Schaller Res Grp Neuropeptides Neuenheimer Feld 307 D-69120 Heidelberg;

    German Canc Res Ctr Schaller Res Grp Neuropeptides Neuenheimer Feld 307 D-69120 Heidelberg;

    German Canc Res Ctr Schaller Res Grp Neuropeptides Neuenheimer Feld 307 D-69120 Heidelberg;

    CNRS 8 Allee Gen Rouvillois F-67000 Strasbourg France;

    CNRS 8 Allee Gen Rouvillois F-67000 Strasbourg France;

    Heidelberg Univ Dept Neurobiol Neuenheimer Feld 364 D-69120 Heidelberg Germany;

    Univ Bonn Med Ctr Dept Psychiat Sigmund Freud Str 25 D-53105 Bonn Germany;

    Heidelberg Univ Dept Gen Psychiat Ctr Psychosocial Med Vossstr 4 D-69115 Heidelberg Germany;

    Heidelberg Univ Interdisciplinary Neurobehav Core INBC Neuenheimer Feld 515 D-69120 Heidelberg;

    CNRS 8 Allee Gen Rouvillois F-67000 Strasbourg France;

    Max Planck Inst Med Res Jahnstr 29 D-69120 Heidelberg Germany;

    Max Planck Inst Med Res Jahnstr 29 D-69120 Heidelberg Germany;

    Charite Neurocure Virchowweg 6 D-10117 Berlin Germany;

    Max Planck Inst Med Res Jahnstr 29 D-69120 Heidelberg Germany;

    Heidelberg Univ Dept Neurobiol Neuenheimer Feld 364 D-69120 Heidelberg Germany;

    CNRS 8 Allee Gen Rouvillois F-67000 Strasbourg France;

    German Canc Res Ctr Schaller Res Grp Neuropeptides Neuenheimer Feld 307 D-69120 Heidelberg;

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  • 正文语种 eng
  • 中图分类 神经病学;
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