Alpha-fetoprotein protects the developing female mouse brain from masculinization and defeminization by estrogens

Two clearly opposing views exist on the function of alpha-fetoprotein (AFP), a fetal plasma protein that binds estrogens with high affinity, in the sexual differentiation of the rodent brain. AFP has been proposed to either prevent the entry of estrogens or to actively transport estrogens into the developing female brain. The availability of Afp mutant mice (Afp-/-) now finally allows us to resolve this longstanding controversy concerning the role of AFP in brain sexual differentiation, and thus to determine whether prenatal estrogens contribute to the development of the female brain. Here we show that the brain and behavior of female Afp-/- mice were masculinized and defeminized. However, when estrogen production was blocked by embryonic treatment with the aromatase inhibitor 1,4,6-androstatriene-3,17- dione, the feminine phenotype of these mice was rescued. These results clearly demonstrate that prenatal estrogens masculinize and defeminize the brain and that AFP protects the female brain from these effects of estrogens. © 2006 Nature Publishing Group.

The temporal dynamics of metacognition: Dissociating task-related activity from later metacognitive processes

In recent years, neuroscience research spent much effort in revealing brain activity related to metacognition. Despite this endeavor, it remains unclear exactly when metacognitive experiences develop during task performance. To investigate this, the current study used EEG to temporally and spatially dissociate task-related activity from metacognitive activity. In a masked priming paradigm, metacognitive experiences of difficulty were induced by manipulating congruency between prime and target. As expected, participants more frequently rated incongruent trials as difficult and congruent trials as easy, while being completely unable to perceive the masked primes. Results showed that both the N2 and the P3 ERP components were modulated by congruency, but that only the P3 modulation interacted with metacognitive experiences. Single-trial analysis additionally showed that the magnitude of the P3 modulation by congruency accurately predicted the metacognitive response. Source localization indicated that the N2 task-related activity originated in the ACC, whereas the P3-interplay between task-related activation and metacognitive experiences originated from the precuneus. We conclude that task-related activity can be dissociated from later metacognitive processing.