Individuals decide between alternatives based on their perceived value of the reward associated with each
option. In humans, this value-based decision-making behavior varies by sex and across the menstrual cycle.
However, it is not understood how endogenous sex hormones influence the neural dynamics that underlie
decision-making. 17b-estradiol, the principle estrogenic hormone that varies in expression across the menstrual
cycle, is a compelling candidate because it is known to activate dopaminergic signaling in the nucleus
accumbens, a key center for reward processing in the brain. This work will address two questions: 1) What is
the effect of 17b-estradiol on rats’ value-based decision-making? 2) What is the in vivo mechanism by which
17b-estradiol modulates dopaminergic signaling during value-based decision-making behavior? This project will
address these questions with state-of-the-art tools, including fiber photometry imaging, mass spectrometry, and
cutting-edge computational methods. It will characterize the interactions between 17b-estradiol and dopamine
signaling in rats performing a novel value-based decision-making behavior in naturally cycling females, in
ovariectomized females with and without an exogenous dose of 17b-estradiol, and in males. This proposal will
establish how 17b-estradiol affects the behavioral engagement of the dopaminergic system and the dynamics of
downstream circuits in rats performing a rich, quantifiable value-based decision-making behavior.