Increased GABAergic Efficacy of Central Amygdala Projections to Neuropeptide S Neurons in the Brainstem During Fear Memory Retrieval.
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.
Institute of Physiology I, Westfälische Wilhelms-Universität Münster, Münster, Germany.
Kay
K
Jüngling
Institute of Physiology I, Westfälische Wilhelms-Universität Münster, Münster, Germany.
Maren D
MD
Lange
Institute of Physiology I, Westfälische Wilhelms-Universität Münster, Münster, Germany.
Hanna J
HJ
Szkudlarek
Institute of Physiology I, Westfälische Wilhelms-Universität Münster, Münster, Germany.
Jörg
J
Lesting
Institute of Physiology I, Westfälische Wilhelms-Universität Münster, Münster, Germany.
Frank S
FS
Erdmann
Institute of Physiology I, Westfälische Wilhelms-Universität Münster, Münster, Germany.
Michael
M
Doengi
Department of Neurology, Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Universitätsmedizin Göttingen, Göttingen, Germany.
Sebastian
S
Kügler
Institute of Physiology I, Westfälische Wilhelms-Universität Münster, Münster, Germany.
Hans-Christian
HC
Pape
D000818:Animals; D001933:Brain Stem / Q000166:cytology* / Q000187:drug effects; D050882:CREB-Binding Protein / Q000378:metabolism; D066274:Central Amygdaloid Nucleus / Q000166:cytology*; D002772:Cholera Toxin / Q000378:metabolism; D003214:Conditioning, Classical / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000494:pharmacology; D004399:Dynorphins / Q000494:pharmacology; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D018682:GABA Agents / Q000494:pharmacology; D059330:GABAergic Neurons / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D051745:Protein Kinase C-delta / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism / Q000494:pharmacology
D004268:DNA-Binding Proteins; D018682:GABA Agents; C499942:Grhl3 protein, mouse; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D014157:Transcription Factors; C539972:neuropeptide S, mouse; D004399:Dynorphins; D002772:Cholera Toxin; D050882:CREB-Binding Protein; D051745:Protein Kinase C-delta