A causal role of estradiol in human reinforcement learning.

The sex hormone estradiol is hypothesized to play a key role in human cognition, and reward processing specifically, via increased dopamine D1-receptor signalling. However, the effect of estradiol on reward processing in men has never been established. To fill this gap, we performed a double-blind placebo-controlled study in which men (N = 100) received either a single dose of estradiol (2 mg) or a placebo. Subjects performed a probabilistic reinforcement learning task where they had to choose between two options with varying reward probabilities to maximize monetary reward. Results showed that estradiol administration increased reward sensitivity compared to placebo. This effect was observed in subjects' choices, how much weight they assigned to their previous choices, and subjective reports about the reward probabilities. Furthermore, effects of estradiol were moderated by reward sensitivity, as measured through the BIS/BAS questionnaire. Using reinforcement learning models, we found that behavioral effects of estradiol were reflected in increased learning rates. These results demonstrate a causal role of estradiol within the framework of reinforcement learning, by enhancing reward sensitivity and learning. Furthermore, they provide preliminary evidence for dopamine-related genetic variants moderating the effect of estradiol on reward processing.

Octamer-binding factor 6 (Oct-6/Pou3f1) is induced by interferon and contributes to dsRNA-mediated transcriptional responses.

BACKGROUND: Octamer-binding factor 6 (Oct-6, Pou3f1, SCIP, Tst-1) is a transcription factor of the Pit-Oct-Unc (POU) family. POU proteins regulate key developmental processes and have been identified from a diverse range of species. Oct-6 expression is described to be confined to the developing brain, Schwann cells, oligodendrocyte precursors, testes, and skin. Its function is primarily characterised in Schwann cells, where it is required for correctly timed transition to the myelinating state. In the present study, we report that Oct-6 is an interferon (IFN)-inducible protein and show for the first time expression in murine fibroblasts and macrophages. RESULTS: Oct-6 was induced by type I and type II IFN, but not by interleukin-6. Induction of Oct-6 after IFNbeta treatment was mainly dependent on signal transducer and activator of transcription 1 (Stat1) and partially on tyrosine kinase 2 (Tyk2). Chromatin immunopreciptitation experiments revealed binding of Stat1 to the Oct-6 promoter in a region around 500 bp upstream of the transcription start site, a region different from the downstream regulatory element involved in Schwann cell-specific Oct-6 expression. Oct-6 was also induced by dsRNA treatment and during viral infections, in both cases via autocrine/paracrine actions of IFNalpha/beta. Using microarray and RT-qPCR, we furthermore show that Oct-6 is involved in the regulation of transcriptional responses to dsRNA, in particular in the gene regulation of serine/threonine protein kinase 40 (Stk40) and U7 snRNA-associated Sm-like protein Lsm10 (Lsm10). CONCLUSION: Our data show that Oct-6 expression is not as restricted as previously assumed. Induction of Oct-6 by IFNs and viruses in at least two different cell types, and involvement of Oct-6 in gene regulation after dsRNA treatment, suggest novel functions of Oct-6 in innate immune responses.