Stephanie Cragg - Neuroscience - 'Neuromodulation of striatal dopamine by neuronal and non-neuronal circuits'

The neurotransmitter dopamine in the striatum is critical to our motivated actions, and is dysregulated in disorders spanning from Parkinson’s disease (PD) to addictions. Midbrain dopamine neurons form intriguing structures: they give rise to colossal axonal arbours that are more branched than any other neuron type, providing opportunities for diverse neuromodulators to act on axons to shape dopamine function. We have discovered striatal circuits that can act on dopamine axons to powerfully transform dopamine output. We are working to better understand the diverse range of striatal neuromodulators and circuits, neuronal and non-neuronal, that act on dopamine axons to govern dopamine output, in mouse brain ex vivo in health and their disturbances in mouse models of PD. Potential DPhil projects will join our effort to reveal the striatal modulators and circuits that govern dopamine transmission, and to understand the dynamic signalling profiles of those neuromodulators and circuits. Research techniques involved will include state-of-the-art methods for the direct detection of neurotransmitters and neuromodulators in real-time, such as imaging genetically encoded fluorescent reporters for neuromodulators (e.g. GRAB sensors to detect amines, neuropeptides, lipid transmitters) or cellular activity (calcium and voltage sensors), alongside fast-scan cyclic voltammetry for real-time detection of dopamine and/or neuronal recordings with electrophysiology, in conjunction with methods to manipulate brain and cells (optogenetics, chemogenetics, pharmacology) in ex vivo brain slices from healthy mice and transgenic models of PD.