Dopaminergic mechanisms guiding probabilistic choice

Dopamine, acting via different modes of transmission, is involved in making cost-benefit decisions involving reward uncertainty. Phasic and tonic dopamine contribute to different behavioral strategies by influencing the connectivity and strength of inputs within the cortico-limbic-striatal circuit. Chapter 1 introduces the construct of risk-based decision-making and approaches to studying it before delving into how tonic and phasic dopamine are involved in encoding reward uncertainty and reward prediction error. This chapter also describes the nucleus accumbens (NAc) as a corticolimbic interface innervated by dopamine and the lateral habenula (LHb) as a modulator of dopamine and source of negative reward prediction error. Chapter 2 examines how receptor-selective dopaminergic drugs infused into the NAc influence risk-based decision-making. The D₂ receptor, mainly influenced by tonic dopamine, was not involved in risky choice. Stimulation of the D₁ receptor, presumably by phasic dopamine, optimized decision-making while blockade of this receptor made animals risk-averse. Chapter 3 demonstrates that the LHb is critical for expressing subjective choice preferences. Inactivation of the LHb induced indifference in animals trained on probabilistic and delay discounting tasks. LHb inactivation on a simpler reward magnitude discrimination task and inactivation of closely adjacent areas were without effect, highlighting both the behavioral and anatomical specificity of this effect. Chapter 4 reveals that temporally and behaviorally specific phasic dopamine changes are critical for probabilistic choice biases. Ventral tegmental area stimulation following a risky loss increased risky choice while stimulation of the LHb, or intermediary rostromedial tegmental area, following a risky win decreased risky choice. Chapter 5 integrates these findings with previous literature and proposes ideas for how phasic and tonic dopamine acting in the cortico-limbic-striatal circuit are used to bias choices involving reward uncertainty.Arts, Faculty ofPsychology, Department ofGraduat