The influence of estrogen of hippocampus and amygdala dependent emotional memory

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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.