Disruption of fear memory through dual-hormone gene therapy.

Disruption of fear memory through dual-hormone gene therapy.
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DOI:
10.1016/j.biopsych.2008.09.003
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发表时间:
2009-03-01
影响因子:
10.6
通讯作者:
Sapolsky, Robert M.
Sapolsky, Robert M.
中科院分区:
医学1区
文献类型:
--
作者:
Rodrigues, Sarina M.;Sapolsky, Robert M.

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The basolateral complex of the amygdala (BLA) is uniquely affected by steroid hormones. While glucocorticoids, the adrenal hormones released during stress, increase the excitability of BLA neurons, estrogen decreases it. 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 E 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. 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, while fear learning and post-shock freezing remained intact. These data show that dual gene therapy with ER/GR may be a useful tool for understanding the role of steroid hormones in the storage of traumatic memories.
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