Estrogen and Memory Bias

雌激素和记忆偏差

• 批准号: RGPIN-2016-06653
• 负责人: Brake, Wayne
• 金额: $ 2.04万
• 依托单位: Concordia University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=682333
• 关键词: Estrogen; Memory; Bias

There is extensive evidence, albeit controversial, implicating estrogen and other ovarian hormones such as progesterone in the cognitive performance of women and other female mammals. There is little doubt that these hormones have a modulatory role in learning and cognition, however, the findings in this area may sometimes be contradictory in both the direction and magnitude of effect.******Rats learning to complete a maze can use one of several memory systems. Firstly, they may use several cues from the environment, or allocentric cues, to develop a cognitive map and use this approach to find the reward. This approach is referred to as a place' memory and is mediated predominantly by the hippocampus. Secondly, rats may use egocentric cues to learn where to go to find the reward. In this case, the rats would learn a series of habitual motor responses such as turn left then turn right. This approach is referred to as a response' memory and is mediated predominately by the dorsal striatum, also known as the caudate/putamen******We, along with others, have established that whether a female rat will use a place or response memory system is dependent upon the level of circulating estrogens. Moreover, our most recent findings suggest that memory system bias may be regulated, in part, by estrogen's effects in the prefrontal cortex. These effects are rapid, suggesting that estrogen is acting through receptors other than the classical steroid/genomic receptors.******We have also established that there are three types of membrane receptors localized to the female rat prefrontal cortex. The more recently identified, GPER1, as well as the classical ERalpha and ERbeta, are also found at the membrane of neurons of the frontal cortex. These findings suggest exciting new directions we can take to explore the rapid effects of ovarian hormones on cognition.******The objectives of this proposal are to explore the influence of the female hormones estrogen and progesterone on neuroplasticity (changes in the structure of neuronal contacts), neurotranmission (changes in neurotransmitter release in response to environmental stimuli), and behavior (changes in paradigms testing multiple memory systems in female rats.*****

尽管存在争议，但有大量证据表明，雌激素和其他卵巢激素(如黄体酮)与女性和其他雌性哺乳动物的认知能力有关。毫无疑问，这些激素对学习和认知具有调节作用，然而，这一领域的发现有时可能在影响的方向和大小上相互矛盾。学习完成迷宫的大鼠可以使用几种记忆系统中的一种。首先，他们可能会使用来自环境的几个线索，或分配中心线索，来开发认知地图，并使用这种方法来寻找奖励。这种方法被称为位置记忆，主要通过海马体进行调节。其次，老鼠可能会使用以自我为中心的线索来学习去哪里寻找奖励。在这种情况下，老鼠会学习一系列习惯性的运动反应，比如先左转，然后右转。这种方法被称为反应记忆，主要由背侧纹状体(也称为尾状/壳核)介导。我们与其他人一起证实，雌性大鼠是否会使用场所或反应记忆系统取决于循环中的雌激素水平。此外，我们最新的发现表明，记忆系统的偏见可能在一定程度上受到雌激素在前额叶皮质的影响。这些作用是迅速的，这表明雌激素是通过经典的类固醇/基因组受体以外的受体起作用的。*我们还发现，有三种类型的膜受体定位于雌性大鼠的前额叶皮质。最近发现的GPER1以及经典的ERa和ERbeta，也在额叶皮质的神经元膜上被发现。这些发现为我们探索卵巢激素对认知的快速影响提供了令人振奋的新方向。*这项建议的目的是探索女性激素雌激素和孕酮对神经可塑性(神经元接触结构的变化)、神经传递(神经递质释放对环境刺激的反应的变化)和行为(测试雌性大鼠多个记忆系统的范式的变化)的影响。