Investigating midbrain dopamine neuron dynamics during decision-making

Abstract

We are faced with decisions on a daily basis - many are simple, such as choosing to drink water when thirsty, whilst others require multi-step evaluation and constant updating of predictions for the future. It was previously assumed that decision-making was a largely cortical process. More recently, in vivo imaging techniques, such as fiber photometry, shone a light onto the significant roles that subcortical structures, such as the basal ganglia, play in decision-making. Midbrain dopamine neurons (mDANs) within the basal ganglia are now thought to facilitate behaviours inextricably linked to choice, such as reward prediction error, motor control and reinforcement learning.

Within this thesis, subpopulations of mDAN are classified based on their projection targets in the striatum and molecular marker profiles. In addition, the intracellular calcium sensor GCaMP6f was expressed in distinct mDAN subpopulations, then their activities were measured with fiber photometry whilst mice performed a novel decision-making task. Activity within mDANs projecting to separate striatal subregions differed significantly during aspects of decision-making. Roles in encoding temporal difference learning and habitual choice are implicated for two mDAN subpopulations. Further, the roles of mDANs projecting to the dorsal striatum and nucleus accumbens core in facilitating goal-directed and Pavlovian behaviour are called into question.

This research provides a novel method of categorising mDAN subpopulations, alongside contributing to current knowledge on which aspects of decision-making are encoded by each population. In addition, an alternative outlook on assessment of associative learning and choice behaviour in rodents, using a decision-making task that does not necessitate rigorous pre-training is provided.

Date of Award	30 Sept 2025
Original language	English
Awarding Institution	University of Bristol
Supervisor	Paul Dodson (Supervisor)