Abstract
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.
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Acknowledgements
We thank Julia Schröer, Elke Naß, Petra Berenbrock, Birgit Herrenpoth, Angelika Klinge, and Svetlana Kiesling for excellent technical assistance. We thank Dr Philippe Coulon for critical reading of the manuscript. Transgenic NPS-EGFP mice were a kind gift of Professor Rainer Reinscheid (University of California, Irvine, CA, USA).
Author Contributions
All experiments were performed at the Institute of Physiology I, Westfälische Wilhelms-Universität at Münster, Germany, and at the Department of Neurology, University Medicine Göttingen, Center Nanoscale Microscopy and Physiology of the Brain (CNMPB), Göttingen, Germany. Concept and design of the experiments: KJ, H-CP, with contributions from MDL, HJS, and JL. Collection, analysis and interpretation of data: all authors. Writing the article: KJ and H-CP, with contributions from HJS, JL, FSE, SK. All authors approved the final version of the manuscript.
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Jüngling, K., Lange, M., Szkudlarek, H. et al. Increased GABAergic Efficacy of Central Amygdala Projections to Neuropeptide S Neurons in the Brainstem During Fear Memory Retrieval. Neuropsychopharmacol 40, 2753–2763 (2015). https://doi.org/10.1038/npp.2015.125
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DOI: https://doi.org/10.1038/npp.2015.125
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