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.
Rodrigues
Sarina M
SM
Department of Biological Sciences, Stanford University, Stanford, California, USA. sarina@berkeley.edu
Sapolsky
Robert M
RM
D000679:Amygdala / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D003214:Conditioning, Classical / Q000187:drug effects; D005239:Fear; D015316:Genetic Therapy; D008297:Male; D008568:Memory / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D011960:Receptors, Estrogen / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism; D019076:Transgenes
D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid