Neuronal excitability and CREB as mediators of stress and the deficit of the extinction of aversive contextual memory: deciphering a glucocorticoid-dependent mechanism in the amygdala

Abstract

Aversive memory dysregulation is crucial in stress or anxiety disorders, such as Post Traumatic Stress Disorder (PTSD), and the extinction of the patient's traumatic memories is part of its treatment. The mechanisms by which an aversive memory is extinguished are not fully understood; however, stress is an essential modulator of these processes and can, among other consequences, cause a deficit in the extinction of such memories. The action of glucocorticoid hormone (GC), the primary stress mediator, on the basolateral amygdala complex (BLA), a structure responsible for attributing emotional valence to memories, is essential in this context. Furthermore, studies have shown that increased neuronal excitability and CREB transcription factor activity are crucial characteristics for recruiting a specific group of neurons at the expense of neighboring neurons. We have shown that two hours of restraint cause a deficit of extinction of the contextual fear memory 10 days after stress via increased GR signaling in the BLA. In addition to the apparent relationship between corticosterone (CORT - murine GC) and aversive memory processes, electrophysiology has shown that increasing CORT signaling in the BLA promotes neuronal excitability in this nucleus. However, no studies show the relationship between CORT-GR signaling, CREB, and neuronal excitability in BLA. Thus, we will investigate whether the effect of stress on the fear memory extinction deficit in mice is due to alterations in the excitability of BLA neurons mediated by GR and CREB signaling. (AU)