Investigating the mechanisms underlying cholinergic regulation of dopamine release

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The neurotransmitter dopamine plays a fundamental role in regulating motor and motivational functions. Disruptions to its signalling underlie several psychomotor disorders, including Parkinson's disease, and addiction disorders. Interestingly, dopamine neurons form highly branched and complex axons, generating a surprisingly high number of synapses, bigger than most other neurons in the central nervous system. These peculiar features suggest that the correspondence between dopamine neuron activation and neurotransmitter release at the synapse is a complex process, regulated by local axonal mechanisms. It is known that a major modulator is acetylcholine, which acts to gate dopamine release at nicotinic acetylcholine receptors localised on dopaminergic axons. These receptors are also the target of exogenous substances, such as nicotine. Despite the high relevance, the underlying mechanisms through which these nicotinic receptors control dopamine release have not been fully unveiled. It is therefore fundamental to understand in deeper detail how this pathway influences dopamine release in the brain, in order to develop potential strategies when such pathway is dysregulated, such as in addiction disorders. This project aims at better defining the modalities of nicotinic receptor regulation of dopamine release and at identifying specific pathways that could be acting downstream of these receptors. We will adopt a rodent model and electrochemical techniques (fast-scan cyclic voltammetry, amperometry) for the detection of released dopamine to shed light on such fundamental questions.BBSRC priority areas: The proposed research project addresses the BBSRC cross-council priorities of brain science and mental health, together with a research approach consistent with the BBSRC priority area of replacement, refinement and reduction (3Rs) of animal use in research, welfare of managed animals and bioscience underpinning health.