Disruption of Fear Memory Through Dual-Hormone Gene Therapy

Background: The basolateral complex of the amygdala (BLA) is uniquely affected by steroid hormones. Whereas glucocorticoids (GCs)the adrenal hormones released during stress-increase the excitability of BLA neurons, estrogen decreases it. Methods: In this study, we used a vector designed to express a chimeric gene that contains the GC-binding domain of the GC receptor (GR) and the DNA binding domain of the estrogen receptor (ER) (ER/GR) in infected neurons; as a result, it transduces GC signals into estrogenic ones. We microinfused ER/GR bilaterally into the BLA of rats to determine whether it would impair fear conditioning, a valuable BLA-dependent paradigm for studying the neural basis of emotional memory. Results: Expression of ER/GR in the BLA caused robust expression of the transgene and a significant disruption of both auditory and contextual long-term fear memory consolidation, whereas fear learning and post-shock freezing remained intact. Conclusions: These data show that dual gene therapy with ER/GR might be a useful tool for understanding the role of steroid hormones in the storage of traumatic memories.