Interaction between attentional signals and dopamine error prediction: focus on midbrain dopaminergic projections to prefrontal cortex. (360G-Wellcome-202054_Z_16_Z)

Midbrain dopamine is implicated in motivation and attentional processes related to error prediction. However, the dominant model of dopamine error prediction advanced over the last two decades is at odds with key behavioural observations and recent theories of attention suggest a role for top-down cortical control over error prediction. This leaves open the question about how the dopamine signal interacts with these top-down mechanisms. This proposal exploits recent advances in optical approaches to brain function which now make this question tractable using rat behavioural tasks. Firstly, I will use fibre photometry to record from dopaminergic projections to medial prefrontal cortex in a classical discrimination task. I will determine whether, in contrast to the canonical dopamine error prediction model, these projections represent both positive and negative prediction error with increased activity. Secondly I will carry out a causal experiment using optogenetic inhibition of prefrontal vs. nucleus accumbens dopaminergic projections in a blocking behavioural paradigm. This experiment will determine whether these projections differ in their contributions to error prediction. This work will delineate novel mechanisms of dopamine reward prediction with implications for our understanding of the fundamental nature of attention and motivation.