Opposing Effects of Stress on Memory Formation and Plast

描述（改编自申请人摘要）：男性和女性是 有着独特的认知能力和情绪反应 女性 大鼠获得经典的条件性眨眼反应比男性快 大鼠 尽管在无压力条件下表现更好，但女性 因先前暴露而在获得条件反应方面严重受损 一个有压力的事件，而男性是便利的。 该基金建议 实验以确定神经元，突触和分子机制 负责1）促进学习的男性与受损 女性在暴露于压力和情绪事件后的学习，以及 2)女性在无压力条件下的表现增强。 的 拟议的实验将解决以下问题。 （一）压力 诱导依赖雌激素的女性学习障碍， 孕酮和糖皮质激素的相互作用？ （二）杏仁核 必要的压力引起的损害学习的女性和他们的 在无压力条件下提高性能？ （三）压力是否诱发 对杏仁核神经元兴奋性的影响与性别有关 记忆形成的差异？ （四）压力是否会对 杏仁核中的棘/突触密度与性别差异相关 在记忆形成中？ 压力和性别对突触密度有影响吗 与树突棘mRNA分布相关的学习， 杏仁核的神经元 方法将包括行为训练， 短暂损伤和显微注射，多单位记录，高尔基体 浸渍和高分辨率原位杂交。 女性代表 超过50%的人口，但他们却远远 在生物医学研究中的代表性不足。 尽管缺乏关注， 最近的证据表明，雌激素是有效的治疗 阿尔茨海默氏病，一种以认知和行为异常为特征的毁灭性疾病， 情绪反应和杏仁核退化 拟议 实验与临床相关，因为它们解决了雌激素如何 有助于哺乳动物大脑中有效的记忆形成。 在 此外，它们与创伤后应激障碍（PTSD）有关， 以持续的行为和神经后果为特征的疾病， 紧张的经历

DESCRIPTION (Adapted from applicant's abstract): Males and females are known to have distinct congitive capacities and emotional responses. Female rats acquire a classically conditioned eye blink response faster than male rats. Despite enhanced performance under unstressed conditions, females are severely impaired in acquiring the conditioned response by previous exposure to a stressful event, while males are facilitated. This grant proposes experiments to identify the neuronal, synaptic and molecular mechanisms responsible for 1) the facilitated learning in males versus the impaired learning in females after exposure to a stressful and emotional event, and 2) the enhanced performance of females under unstressed conditions. The proposed experiments will address the following questions. I) Is the stress induced impairment of learning in females dependent on estrogen and progesterone and an interaction with glucocorticoids? II) Is the amygdala necessary for the stress induced impairment of learning in females and their enhanced performance under unstressed conditions? III) Are stress induced effects on neuronal excitability in the amygdala associated with the sex differences in memory formation? IV) Are stress induced effects on spine/synaptic density in the amygdala associated with the sex differences in memory formation? V) Are the stress and sex effects on synaptic density and learning associated with the distribution of mRNA to dendritic spines in neurons of the amygdala? Methodologies will include behavioral training, transient lesioning and microinjections, multiple unit recording, Golgi impregnation and high resolution in situ hybridization. Females represent over 50 percent of the human population, yet they are vastly underrepresented in biomedical research. Despite the lack of attention, recent evidence suggests that estrogen is effective in the treatment of Alzheimer's disease, a devastating disease marked by abnormal cognitive and emotional responses and deterioration of the amygdala. The proposed experiments are clinically relevant because they address how estrogen contributes to the effective memory formation in the mammalian brain. In addition, they are relevant to post traumatic stress disorder (PTSD), a disease marked by the persistent behavioral and neuronal consequences of stressful experience.