Gordon W Arbuthnott
Scientific Tracks Abstracts: J Neurol Neurophysiol
Aimed at the subthalamic nucleus (STN) or the Globus Pallidus Internus (GPI), deep brain stimulation (DBS) has become a useful treatment for Parkinsonian patients whose drug tolerance has made L-DOPA no longer effective. The underlying mechanism is still in debate although several model systems suggest that the target is neither GPI nor STN but the corticofugal fibres close to them. Although this explanation seems at first bizarre, it does so only in the context of a very static model of basal ganglia function that assumes + and - signs of neuronal activity rather than accepting important neuronal network interactions. Recent experiments looking at striatal firing patterns suggest that the consequences of dopamine loss concern the pattern of network activity. Neurons of mouse striatal slices with a previous dopamine (DA) input damage fire together in large groups. Neurons with both DA receptor subtypes D1 and D2 are equally involved in the modified activity. When intact striatal neurons were optogenetically excited so that they fired collectively, the animals turned in circles as they do when the dopamine input is destroyed. These results led us to conclude that in the absence of dopamine the collective firing of many neurons is the cause of motor disturbances. It seems that by imposing a non-oscillatory mode of firing by direct activation of corticofugal fibres, DBS disrupts congruent firing and improves the movement disorder that underlies the symptoms of Parkinson?s disease
Gordon W Arbuthnott having completed both BSc and PhD from Aberdeen University and Postdoctoral studies in the Karolinska Institute in Stockholm, Professor Arbuthnott worked for many years in the University of Edinburgh, with the UK Medical Research Council and as a Professor of Neuroscience. He moved to OIST soon after it was formed, contributing to its development as an International Graduate University. His interest in dopamine stems from early work on 6-hydroxydopamine as a method of removing dopamine cells in rodents and his interest in the consequences, for the animals and hence for PD patients, has occupied him for his entire career.
