Increased GABAergic Efficacy of Central Amygdala Projections to Neuropeptide S Neurons in the Brainstem During Fear Memory Retrieval

Kay Jüngling; Maren D Lange; Hanna J Szkudlarek; Jörg Lesting; Frank S Erdmann; Michael Doengi; Sebastian Kügler; Hans-Christian Pape

doi:10.1038/npp.2015.125

Increased GABAergic Efficacy of Central Amygdala Projections to Neuropeptide S Neurons in the Brainstem During Fear Memory Retrieval

Neuropsychopharmacology. 2015 Nov;40(12):2753-63. doi: 10.1038/npp.2015.125. Epub 2015 May 4.

Authors

Kay Jüngling¹, Maren D Lange¹, Hanna J Szkudlarek¹, Jörg Lesting¹, Frank S Erdmann¹, Michael Doengi¹, Sebastian Kügler², Hans-Christian Pape¹

Affiliations

¹ Institute of Physiology I, Westfälische Wilhelms-Universität Münster, Münster, Germany.
² Department of Neurology, Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Universitätsmedizin Göttingen, Göttingen, Germany.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain Stem / cytology*
Brain Stem / drug effects
CREB-Binding Protein / metabolism
Central Amygdaloid Nucleus / cytology*
Cholera Toxin / metabolism
Conditioning, Classical / drug effects
DNA-Binding Proteins / metabolism
DNA-Binding Proteins / pharmacology
Dynorphins / pharmacology
Fear / drug effects
Fear / physiology*
GABA Agents / pharmacology
GABAergic Neurons / physiology*
Gene Expression Regulation / drug effects
Gene Expression Regulation / genetics
Mental Recall / drug effects
Mental Recall / physiology*
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neural Pathways / physiology*
Neuropeptides / genetics
Neuropeptides / metabolism*
Neurotransmitter Agents / pharmacology
Protein Kinase C-delta / metabolism
Synaptic Transmission / drug effects
Synaptic Transmission / genetics
Transcription Factors / metabolism
Transcription Factors / pharmacology

Substances

DNA-Binding Proteins
GABA Agents
Grhl3 protein, mouse
Neuropeptides
Neurotransmitter Agents
Transcription Factors
neuropeptide S, mouse
Dynorphins
Cholera Toxin
CREB-Binding Protein
Protein Kinase C-delta