Jüngling Kay, Lange Maren D, Szkudlarek Hanna J, Lesting Jörg, Erdmann Frank S, Doengi Michael, Kügler Sebastian, Pape Hans-Christian
Institute of Physiology I, Westfälische Wilhelms-Universität Münster, Münster, Germany.
Department of Neurology, Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Universitätsmedizin Göttingen, Göttingen, Germany.
Neuropsychopharmacology. 2015 Nov;40(12):2753-63. doi: 10.1038/npp.2015.125. Epub 2015 May 4.
The canonical view on the central amygdala has evolved from a simple output station towards a highly organized microcircuitry, in which types of GABAergic neurons in centrolateral (CeL) and centromedial (CeM) subnuclei regulate fear expression and generalization. How these specific neuronal populations are connected to extra-amygdaloid target regions remains largely unknown. Here we show in mice that a subpopulation of GABAergic CeL and CeM neurons projects monosynaptically to brainstem neurons expressing neuropeptide S (NPS). The CeL neurons are PKCδ-negative and are activated during conditioned fear. During fear memory retrieval, the efficacy of this GABAergic influence on NPS neurons is enhanced. Moreover, a large proportion of these neurons (~50%) contain prodynorphin and somatostatin, two neuropeptides inhibiting NPS neurons. We conclude that CeL and CeM neurons inhibit NPS neurons in the brainstem by GABA release and that efficacy of this connection is strengthened upon fear memory retrieval. Thereby, this pathway provides a possible feedback mechanism between amygdala and brainstem routes involved in fear and stress coping.
关于中央杏仁核的传统观点已从一个简单的输出站演变为一个高度有组织的微电路，其中中央外侧（CeL）和中央内侧（CeM）亚核中的γ-氨基丁酸能（GABAergic）神经元类型调节恐惧表达和泛化。这些特定的神经元群体如何与杏仁核外的目标区域相连，在很大程度上仍然未知。在这里，我们在小鼠中发现，GABAergic CeL和CeM神经元的一个亚群单突触投射到表达神经肽S（NPS）的脑干神经元。CeL神经元是蛋白激酶Cδ阴性的，并且在条件性恐惧期间被激活。在恐惧记忆检索期间，这种GABAergic对NPS神经元的影响效力增强。此外，这些神经元中的很大一部分（约50%）含有前强啡肽和生长抑素，这两种神经肽抑制NPS神经元。我们得出结论，CeL和CeM神经元通过释放GABA抑制脑干中的NPS神经元，并且这种连接的效力在恐惧记忆检索时增强。因此，这条通路提供了一种可能的杏仁核与参与恐惧和应激应对的脑干通路之间的反馈机制。
