The brain’s ability to regulate dopamine release is critical for motivation, movement, and reinforcement learning, and becomes disrupted in disorders such as Parkinson’s disease and addiction disorders. A balance between striatal dopamine and acetylcholine has long been considered important, but there has been much debate about how or whether acetylcholine supports or hinders dopamine output.
In a recent study published in Nature Neuroscience, work led by Dr Yanfeng Zhang, a former postdoctoral researcher in the Cragg lab now a lecturer at the University of Exeter, and Professor Stephanie Cragg, revealed that cholinergic interneurons in the striatum operate a dynamic, ongoing scaling depression of striatal dopamine release. A background of activation of striatal nicotinic receptors transiently limits how dopamine axons can be reactivated in response to subsequent incoming stimuli.
Professor Cragg commented 'These findings challenge existing thinking about how acetylcholine shapes dopamine output, and provide us with fundamental new perspectives on the principles of neuromodulation that shape dopamine signalling. They also shed light on whether turning nicotinic receptors on or off might be most beneficial for potential treatments of dopamine-related disorders, such as Parkinson’s disease'.
DPAG members Professors Ed Mann and Armin Lak were among the key collaborators. We are very grateful to all our collaborators and funding bodies. The work was supported by Aligning Science Across Parkinson’s through the Michael J. Fox Foundation, as well as the Medical Research Council, building on prior work funded by Parkinson’s UK.
You can read the paper here