The influence of estrogen of hippocampus and amygdala dependent emotional memory

本研究旨在探讨雌激素对中性和情绪情景记忆的影响，以及与之相关的神经系统，如海马和杏仁核。这些研究问题是基于大量的动物研究，这些研究表明，在过去的20年里，雌激素对海马突起的实质性影响。雌激素促进例如LTP的诱导和海马中的突触发生。与这些细胞过程一致，雌激素影响动物海马依赖性学习和记忆。当雌激素在编码后给药时，它对巩固也有有益的影响。然而，越来越多的证据表明，剂量反应函数遵循倒U形，即较高剂量的雌激素可能具有不利影响。近年来，研究发现雌激素对杏仁核形态和功能的影响。特别是，雌激素似乎降低了杏仁核的敏感性，与许多关于雌激素核心作用的动物研究形成鲜明对比的是，令人惊讶的是，很少有人类数据，特别是神经影像学研究。因此，目前的建议旨在探索雌激素的核心作用，首次在安慰剂对照研究中，绝经前妇女使用功能性磁共振成像。为此，雌激素水平将升高到黄体期以及最大值，自然周期妇女在早期卵泡，低激素周期阶段排卵前的水平。因此，剂量反应函数可以在生理水平内导出。将探索雌激素敏感性中互补的、基于遗传的个体间差异，并与不同雌激素水平的影响进行比较。将使用包括中性和情感刺激编码的记忆范式来研究海马和杏仁核依赖性学习过程。虽然中性刺激的编码依赖于海马体，但情绪刺激的记忆形成是基于杏仁核与海马体的相互作用。这两种结构都与编码和提取密切相关，但它们对这两个过程的贡献在每种情况下都有根本的不同。 因此，本研究拟采用两种平行的相移范式，分别探讨雌激素对中性信息和情绪信息的编码和提取的影响。在一个伴随的行为实验中，将探讨学习后雌激素如何影响巩固。最后，在另外两个行为实验中，将进一步说明雌激素对情绪处理和记忆的影响。

The current project aims to explore the influence of estrogen on neutral and emotional episodic memory, as well as its neural correlates, i.e. hippocampus and amygdala. These research questions are based on a large body of animal studies that have shown the substantial impact of estrogen on hippocampal processes in the last 20 years. Estrogen facilitates for instance the induction of LTPs and the synaptogenesis in the hippocampus. Consistent with these cellular processes, estrogen affects hippocampus dependent learning and memory in animals. When estrogen is administered after encoding it has also beneficial effects on consolidation. However, evidence accumulated that the dose-response-function follows an inverted u-shape, i.e. higher doses of estrogen might have detrimental effects. Recently, in addition effects of estrogen on amygdala morphology and function were reported. In particular, estrogen seems to reduce the sensitivity of the amygdala.In sharp contrast to the many animal study on the central role of estrogen, there are surprisingly few human data, in particular neuroimaging studies. The current proposal aims therefore to explore the central role of estrogen for the first time in a placebo controlled study in premenopausal women using functional magnetresonancetomography. To this end, the estrogen level will be elevated pharmacologically to the luteal as well as maximal, pre-ovulatory level in natural cycling women in the early follicular, low hormone cycle phase. Thus, the dose-response function can be derived within physiological levels. Complementary, genetic based interindividual differences in the estrogen sensitivity will be explored and compared with the effects of different estrogen levels.Hippocampus and amygdala dependent learning processes will be studied using a memory paradigm that comprises the encoding of neutral as well as emotional stimuli. While the encoding of neutral stimuli depends on the hippocampus, the memory formation of emotional stimuli is based on an interaction of the amygdala with the hippocampus. Both structures are critically involved in encoding and retrieval but their contribution to both process differs in each case fundamentally. Therefore it is planned to employ phase shifted two parallel versions of the paradigm to explore exclusively the influence of estrogen on encoding and retrieval of neutral and emotional information respectively. In an accompanying behavioral experiment it will be explored how post-learning estrogen affect consolidation. Finally, in two additional behavioral experiments effects of estrogen on emotional processing and memory will be further specified.