Abstract
The posttraumatic stress disorder is marked by an impaired ability to extinct fear memory acquired in trauma. Although previous studies suggest that fear extinction depends on the function of the amygdala, the underlying mechanisms are unclear. We found that NRG1 receptors (ErbB4) were abundantly expressed in the intercalated cells mass of amygdala (ITC). The NRG1-ErbB4 pathway in the ITC promotes fear extinction. The NRG1-ErbB4 pathway in the ITC did not affect excitatory input to ITC neurons from BLA neurons but increased feed-forward inhibition of (the central medial nucleus of the amygdala) CeM neurons through increased GABAergic neurotransmission of ITC neurons. We also found that the NRG1-ErbB4 signaling pathway in ITC might regulate fear extinction through P/Q-type voltage-activated Ca2+ channels (VACCs) but not through L- or N-type VACCs. Overall, our results suggest that the NRG1-ErbB4 signaling pathway in the ITC might represent a potential target for the treatment of anxiety disorders.
Highlights
Healthy individuals can process fearful and other emotional stimuli and extinguish fear in situations that are no longer threatening
We observed that ErbB4 was found primarily in GABAergic interneurons in the basolateral nucleus of the amygdala (BLA) [24], there is no morphological or behavioral evidence to show whether ErbB4 is expressed in GABAergic intercalated amygdala (ITC) neurons or is involved in the regulation of fear extinction
Previous studies have shown that fear extinction depends on an increased inhibition of central medial nucleus of the amygdala (CeM) neurons mediated by enhanced activity of ITC neurons [36]
Summary
Healthy individuals can process fearful and other emotional stimuli and extinguish fear in situations that are no longer threatening. Patients with posttraumatic stress disorder (PTSD) or other anxiety disorders have difficulty extinguishing fearful memories. Pavlovian fear conditioning is a classical model for research on anxiety disorders in the laboratory [1][2, 3]. Fear conditioning resembles PTSD [4, 5]. An animal is given the conditioned stimulus (CS) repeatedly without the unconditioned stimulus (US) [6]. Understanding the mechanisms underlying fear memory extinction is important for understanding the mechanism of fear inhibition and may help to improve the treatment of anxiety disorders
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