Investigating the regulation of mesolimbic dopamine during reward-guided action selection and inhibition
Lead Research Organisation:
University of Oxford
Department Name: Experimental Psychology
Abstract
A substantial body of work has implicated mesolimbic dopamine as an integral component of reward-guided decision-making. Midbrain dopamine activity and release in the nucleus accumbens (NAcc) scales with predictions of future reward, and manipulations of dopamine in the NAcc can change how animals respond to and approach reward-predicting cues.
However, in certain contexts, it can actually be advantageous to refrain from responding in the presence of a reward opportunity in order to achieve the greater future benefits. Crucially, we (1) have recently shown that in exactly such situations of action restraint, dopamine reward value signals in the NAcc are suppressed compared to when they need to make a response to gain reward. This finding dovetails with a number of other studies that have shown that mesolimbic dopamine, and reward-guided behaviour, can be contextually regulated by afferent brain regions, in concert with local neuromodulatory control (e.g., 2). It also aligns with increasing interest, including from Lundbeck teams, in the idea that an imbalance in mesolimbic dopamine and dysfunctional reward processing may be a transdiagnostic hallmark of many neuropsychiatric disorders (3,4).
The key unresolved questions now are where and under what circumstances this regulation of dopamine occurs, and how this regulation supports appropriate reward-guided behaviour. The project will address these critical issues by measuring and manipulating mesolimbic dopamine in rodents performing sophisticated reward-based behavioural tasks.
The collaborative studentship brings together researchers in Experimental Psychology at the University of Oxford at the forefront of research into how neurochemistry influences reward-guided behaviours with scientists at Lundbeck who have expertise in translational research and extensive knowledge in dopamine pharmacology and alterations in neuropsychiatric disease states.
However, in certain contexts, it can actually be advantageous to refrain from responding in the presence of a reward opportunity in order to achieve the greater future benefits. Crucially, we (1) have recently shown that in exactly such situations of action restraint, dopamine reward value signals in the NAcc are suppressed compared to when they need to make a response to gain reward. This finding dovetails with a number of other studies that have shown that mesolimbic dopamine, and reward-guided behaviour, can be contextually regulated by afferent brain regions, in concert with local neuromodulatory control (e.g., 2). It also aligns with increasing interest, including from Lundbeck teams, in the idea that an imbalance in mesolimbic dopamine and dysfunctional reward processing may be a transdiagnostic hallmark of many neuropsychiatric disorders (3,4).
The key unresolved questions now are where and under what circumstances this regulation of dopamine occurs, and how this regulation supports appropriate reward-guided behaviour. The project will address these critical issues by measuring and manipulating mesolimbic dopamine in rodents performing sophisticated reward-based behavioural tasks.
The collaborative studentship brings together researchers in Experimental Psychology at the University of Oxford at the forefront of research into how neurochemistry influences reward-guided behaviours with scientists at Lundbeck who have expertise in translational research and extensive knowledge in dopamine pharmacology and alterations in neuropsychiatric disease states.
