Sex specific effects of estrogen on the neural substrates of episodic and fear memory
Final Report Abstract
The most important finding with respect to the two main experiments, reinforcement learning and spatial memory/navigation, that we conducted in the MRI-scanner is that we were able to translate the findings from animal studies to humans and observed effects of E2 on spatial memory and reward based learning. For the latter one we also observed robust differences in the underlying neural activity, the fMRI data related to spatial memory and navigation are still analyzed. These results suggest that we reasonably adjusted the originally proposed paradigms based on the results of our previous project - without changing the overarching research questions. Moreover, our results with respect to E2’s effect on navigation behavior point to the entorhinal cortex, an area for which studies on E2’s action are nearly completely missing in animals - despite the abundant E2-receptors (exception: Gervais et al., 2013). Our results might inspire animal studies to explore E2’s effects in this area also on the cellular level. The acquired large data set on mental rotation in men and women with and without E2 will complement our data set covering a wide range of E2 levels in women. Together, it will be possible to answer the long-standing question if and to what degree E2 and organizational sex difference contribute to the observed robust sex difference in mental rotation. The results of the two experiments on E2’s effect on affective processing, however, have to be evaluated differently. Whereas the null-finding with respect to E2 modulation of fear memory consolidation might be well explained by the relatively slow increase in E2 levels compared to the animal experiments, the absence of a behavioral effect of elevated E2 levels in the virtual elevated plus maze might indicate that E2 act indeed if at all only very subtly anxiolytic because the heatmap-analysis is very sensitive. With respect to the applied questions, i.e. whether sex differences in the prevalence and severity of affective and addictive disorders, are caused by activational effects of estrogen or organizational sex differences (in addition to cultural influences) we clearly see enhancing effects of E2 on dopaminergic neurotransmission but not affective processing, whereas organizational sex differences affect both. Taken together, when all experiments of the current project will be fully analyzed and published, they will substantially advance our understanding of E2’s effects and organizational sex differences in the human brain and behavior.
Publications
- Joue G, Chakroun K, Bayer J, Gläscher J , Zhang L, Fuss J, Hennies N, Sommer T (under review). Sex differences and exogenous estrogen influence learning and brain responses to prediction errors. Neuropsychopharmacology
Joue G, Chakroun K, Bayer J, Gläscher J , Zhang L, Fuss J, Hennies N, Sommer T
(See online at https://doi.org/10.1093/cercor/bhab334) - (2018). Susceptibility distortion correction for fMRI. Proc. Intl. Soc. Mag. Reson. Med. 26
Joue G, Sommer T, Mohammadi S
