Parsing dopamine's learning and motor functions

ended

Appropriate selection of situation-appropriate behaviour requires both learning and motor control. Release of the neurotransmitter dopamine in the striatam is crucially involved in both of these processes. However, previous work investigated learning and motor functions of dopamine in isolation. To fully understand dopamine function and dysfunction, it is imperative to take both learning and motor control into account. Striatal dopamine release is thought to encode a reward prediction error, the discrepancy between expected and obtained outcome, as well as promote movement. Dopamine release optimises and drives behaviour by modulating the activity of striatal medium spiny neurons (MSNs) and their downstream neural pathways. Binding of dopamine to type-1 and type-2 dopamine receptor-expressing MSNs differentially modulate intracellular signalling cascades, increasing or decreasing phosphorylation of protein kinase A (PKA), respectively. Differential modulation of PKA activity is thought to underlie learning and motor control, ultimately driving behaviour. Importantly, dopamine’s influence on MSNs is functionally disparate between limbic, associative, and sensorimotor domains, and it is hypothesised that these regions differentially encode learning and movement. Here, I aim to discern the entanglement of dopamine functions by employing a powerful behavioural task that differentiates between learning and movement, while 1) simultaneously recording dopamine release in distinct striatal domains, and 2) recording the activity type-1 or type-2 MSNs using a novel, cutting-edge tool to detect real-time PKA activity. The complementary power of these innovations will enable me to drive forward the current understanding of dopamine’s function by combining state-of-the-art neuroscience techniques, elucidating the entanglement of dopamine in learning and motor control on behaviour.