Opposing Effects of Stress on Memory Formation and Plast

描述(改编自申请者摘要)：男性和女性 已知具有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雄性快 老鼠。尽管在没有压力的情况下表现更好，但雌性 因先前暴露而获得条件性反应时严重受损 有压力的活动，而雄性则被促进。这项拨款建议 识别神经元、突触和分子机制的实验 负责1)促进男性与受损者的学习 女性在暴露于压力和情绪事件后的学习，以及 (2)女性在非应激状态下的表现增强。这个 拟议的实验将解决以下问题。I)是压力吗？ 依赖雌激素和雌激素的女性学习障碍 黄体酮和糖皮质激素的相互作用？Ii)是杏仁核 应激所致的学习障碍在女性及其女性中的作用 在非压力条件下增强表现？三)是由压力引起的吗 性别对杏仁核神经元兴奋性的影响 记忆形成的差异？四)应激诱导的影响 杏仁核棘/突触密度与性别差异的关系 在记忆形成过程中？V)应激和性别对突触密度的影响 以及与树突棘的mRNA分布相关的学习 杏仁核的神经元？方法将包括行为训练， 暂时性病变和微量注射、多单元记录、高尔基体 浸渍和高分辨原位杂交。女性代表着 超过50%的人口，但他们是巨大的 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，雌激素在治疗癌症方面是有效的。 阿尔茨海默病，一种毁灭性的疾病，其特征是认知和 情绪反应和杏仁核退化。建议数 实验具有临床意义，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……里面 此外，它们与创伤后应激障碍(PTSD)有关， 一种以持续的行为和神经后果为特征的疾病 充满压力的经历。

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.