Prevention of stress-impaired fear extinction through neuropeptide s action in the lateral amygdala.
Stressful and traumatic events can create aversive memories, which are a predisposing factor for anxiety disorders. The amygdala is critical for transforming such stressful events into anxiety, and the recently discovered neuropeptide S transmitter system represents a promising candidate apt to control these interactions. Here we test the hypothesis that neuropeptide S can regulate stress-induced hyperexcitability in the amygdala, and thereby can interact with stress-induced alterations of fear memory. Mice underwent acute immobilization stress (IS), and neuropeptide S and a receptor antagonist were locally injected into the lateral amygdala (LA) during stress exposure. Ten days later, anxiety-like behavior, fear acquisition, fear memory retrieval, and extinction were tested. Furthermore, patch-clamp recordings were performed in amygdala slices prepared ex vivo to identify synaptic substrates of stress-induced alterations in fear responsiveness. (1) IS increased anxiety-like behavior, and enhanced conditioned fear responses during extinction 10 days after stress, (2) neuropeptide S in the amygdala prevented, while an antagonist aggravated, these stress-induced changes of aversive behaviors, (3) excitatory synaptic activity in LA projection neurons was increased on fear conditioning and returned to pre-conditioning values on fear extinction, and (4) stress resulted in sustained high levels of excitatory synaptic activity during fear extinction, whereas neuropeptide S supported the return of synaptic activity during fear extinction to levels typical of non-stressed animals. Together these results suggest that the neuropeptide S system is capable of interfering with mechanisms in the amygdala that transform stressful events into anxiety and impaired fear extinction.
Institute of Physiology I-Neurophysiology, Westfälische Wilhelms-University Münster, Münster, Germany.
Frédéric
F
Chauveau
Maren Denise
MD
Lange
Kay
K
Jüngling
Jörg
J
Lesting
Thomas
T
Seidenbecher
Hans-Christian
HC
Pape
D000679:Amygdala / Q000187:drug effects* / Q000503:physiopathology; D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005108:Extinction, Psychological / Q000187:drug effects* / Q000502:physiology; D005239:Fear / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D009479:Neuropeptides; C539972:neuropeptide S, mouse