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Parsing dopamine's learning and motor functions

Project description

Insight into the role of dopamine in behaviour

Dopamine is a pleiotropic neurotransmitter that acts as a chemical messenger to assist communication between nerve cells. Dopamine plays a role in movement, learning and attention, among other functions, yet aberrant levels of dopamine have been linked to a spectrum of disorders, including depression and addiction. Funded by the Marie Skłodowska-Curie Actions programme, the RegionalDopamine project aims to delineate the role of dopamine in behaviour that involves both learning and motor processes. Through an innovative behavioural task and the analysis of the downstream pathways of dopamine, researchers will distinguish how dopamine affects learning and motor control, and how it drives behaviour.

Objective

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.

Coordinator

STICHTING AMSTERDAM UMC
Net EU contribution
€ 187 624,32
Address
DE BOELELAAN 1117
1081 HV Amsterdam
Netherlands

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Region
West-Nederland Noord-Holland Groot-Amsterdam
Activity type
Research Organisations
Links
Total cost
No data