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

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 mechanism...

Full description

Saved in:
Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2008-07, Vol.59 (2), p.298-310
Main Authors: Jüngling, Kay, Seidenbecher, Thomas, Sosulina, Ludmila, Lesting, Jörg, Sangha, Susan, Clark, Stewart D., Okamura, Naoe, Duangdao, Dee M., Xu, Yan-Ling, Reinscheid, Rainer K., Pape, Hans-Christian
Format: Article
Language:English
Subjects:
Amygdala - drug effects
Amygdala - physiology
Animals
Anxiety
Behavior
Extinction, Psychological - drug effects
Extinction, Psychological - physiology
Fear - drug effects
Fear - physiology
gamma-Aminobutyric Acid - physiology
Interneurons - drug effects
Interneurons - physiology
Mice
Mice, Inbred C57BL
Mice, Transgenic
MOLNEURO
Neurons
Neuropeptides
Neuropeptides - pharmacology
Rats
Rodents
Synaptic Transmission - physiology
SYSNEURO
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2008.07.002