The influence of estrogen of hippocampus and amygdala dependent emotional memory

目前的项目旨在探索雌激素对中性和情绪性情景记忆的影响，以及它的神经关联，即海马体和杏仁核。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，雌激素对海马区进程产生了实质性的影响。例如，雌激素有助于LTPS的诱导和海马区突触的形成。与这些细胞过程一致，雌激素影响动物的海马体依赖学习和记忆。当雌激素在编码后给予时，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-函数呈倒U形，即较高剂量的雌激素可能会产生有害影响。最近，还报道了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。与许多关于雌激素中心作用的动物研究形成鲜明对比的是，人类数据令人惊讶地少，特别是神经成像研究。因此，目前的建议旨在利用功能性磁共振仪首次在绝经前妇女的安慰剂对照研究中探索雌激素的核心作用。为此，在自然周期的早期卵泡、低激素周期阶段，雌激素水平将从药理上提高到黄体以及排卵前的最高水平。因此，可以在生理水平内推导出剂量-响应函数。我们将探索雌激素敏感性的互补、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。将使用包括中性刺激和情绪刺激编码的记忆范式来研究海马区和杏仁核依赖的学习过程。中性刺激的编码依赖于海马体，而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检索密切相关，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，我们计划使用两种平行的相移范式来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。在随之而来的一项行为实验中，将探索学习后雌激素如何影响巩固。最后，在另外两个行为实验中，将进一步明确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.