PI3K-Akt Signaling in the Basolateral Amygdala Facilitates Traumatic Stress Enhancements in Fear Memory
| Autor: | Negin Mohammadmirzaei, Matt Biddle, Abigail Farkash, Brianna Shultz, Marisa Chamness, Rebecca Della Valle, Dayan Knox, Emily Moulton |
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| Rok vydání: | 2020 |
| Předmět: |
Male
AcademicSubjects/MED00415 fear memory Regular Research Articles Amygdala Extinction Psychological Rats Sprague-Dawley Stress Disorders Post-Traumatic Phosphatidylinositol 3-Kinases single prolonged stress Basolateral amygdala medicine Animals Pharmacology (medical) Fear conditioning Protein kinase B PI3K/AKT/mTOR pathway Phosphoinositide-3 Kinase Inhibitors Pharmacology Behavior Animal Basolateral Nuclear Complex AcademicSubjects/SCI01870 extinction business.industry Traumatic stress PTSD Fear Extinction (psychology) Rats Disease Models Animal Psychiatry and Mental health medicine.anatomical_structure Mental Recall Signal transduction business Proto-Oncogene Proteins c-akt Neuroscience Stress Psychological Signal Transduction |
| Zdroj: | International Journal of Neuropsychopharmacology |
| ISSN: | 1469-5111 1461-1457 |
| Popis: | Background A core symptom of posttraumatic stress disorder is persistent fear memory, which can be defined as fear memory that is resistant to updating, inhibition, or extinction. posttraumatic stress disorder emerges after traumatic stress exposure, but neurobiological mechanisms via which traumatic stress leads to persistent fear memory are not well defined. Akt signaling within the amygdala (Amy) is enhanced with traumatic stress, and phosphatidylinositol kinase 3 (PI3K) activation of Akt within the basolateral Amy (BLA) has been implicated as critical to fear memory formation. These findings raise the possibility that traumatic stress enhances PI3K→Akt signaling in the BLA, which leads to persistent fear memory. Methods To test this hypothesis, rats were exposed to traumatic stress using the single prolonged stress model, and changes in Akt phosphorylation were assayed in the Amy at 0 and 30 minutes after fear conditioning (FC). In a separate experiment, we inhibited PI3K→Akt signaling in the BLA prior to FC and observed the effect this had on acquisition, expression, and extinction of FC in stressed and control rats. Results Enhanced Akt phosphorylation in the Amy at both time points was observed in stressed rats, but not in control rats. PI3K→Akt inhibition in the BLA had no effect on freezing in control rats but decreased freezing during extinction training and testing in stressed rats. Conclusion These findings suggest that PI3K→Akt signaling in the BLA could be a mechanism via which traumatic stress leads to fear memory that is resistant to extinction. |
| Databáze: | OpenAIRE |
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