Sarina M Rodrigues1, Robert M Sapolsky. 1. Department of Biological Sciences, Stanford University, Stanford, California, USA. sarina@berkeley.edu
Abstract
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.
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.
Authors: Jin-Hee Han; Steven A Kushner; Adelaide P Yiu; Christy J Cole; Anna Matynia; Robert A Brown; Rachael L Neve; John F Guzowski; Alcino J Silva; Sheena A Josselyn Journal: Science Date: 2007-04-20 Impact factor: 47.728
Authors: Andrea Nicholas; Carolina D Munhoz; Deveroux Ferguson; Laura Campbell; Robert Sapolsky Journal: J Neurosci Date: 2006-11-08 Impact factor: 6.167
Authors: M B Solomon; A R Furay; K Jones; A E B Packard; B A Packard; A C Wulsin; J P Herman Journal: Neuroscience Date: 2011-12-24 Impact factor: 3.590
Authors: Sarina M Rodrigues; Laura R Saslow; Natalia Garcia; Oliver P John; Dacher Keltner Journal: Proc Natl Acad Sci U S A Date: 2009-11-23 Impact factor: 11.205
Authors: Candace M Raio; Catherine A Hartley; Temidayo A Orederu; Jian Li; Elizabeth A Phelps Journal: Proc Natl Acad Sci U S A Date: 2017-10-02 Impact factor: 11.205
Authors: Eric M Prager; Jennifer Brielmaier; Hadley C Bergstrom; Jennifer McGuire; Luke R Johnson Journal: PLoS One Date: 2010-12-15 Impact factor: 3.240