Neuropeptide S-mediated Control of Fear Expression and Extinction: Role of Intercalated GABAergic Neurons in the Amygdala

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2008 Aug 1

PMID 18667157

Citations 137

Authors

Kay Jungling

Thomas Seidenbecher

Ludmila Sosulina

Jorg Lesting

Susan Sangha

Stewart D Clark

Naoe Okamura

Dee M Duangdao

Yan-Ling Xu

Rainer K Reinscheid

Hans-Christian Pape

Affiliations

Soon will be listed here.

Abstract

A deficient extinction of memory is particularly important in the regime of fear, where it limits the beneficial outcomes of treatments of anxiety disorders. Fear extinction is thought to involve inhibitory influences of the prefrontal cortex on the amygdala, although the detailed synaptic mechanisms remain unknown. Here, we report that neuropeptide S (NPS), a recently discovered transmitter of ascending brainstem neurons, evokes anxiolytic effects and facilitates extinction of conditioned fear responses when administered into the amygdala in mice. An NPS receptor antagonist exerts functionally opposing responses, indicating that endogenous NPS is involved in anxiety behavior and extinction. Cellularly, NPS increases glutamatergic transmission to intercalated GABAergic neurons in the amygdala via presynaptic NPS receptors on connected principal neurons. These results identify mechanisms of NPS in the brain, a key role of intercalated neurons in the amygdala for fear extinction, and a potential pharmacological avenue for treating anxiety disorders.

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