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Conférence mensuelle - Peter Magill / PhD Seminar SeriesThe external globus pallidus in health and Parkinsonism

Abstract :

It is widely held that the cardinal movement difficulties seen in Parkinson’s disease arise from the abnormal firing rates of neurons in the basal ganglia and their partner brain circuits. Electrophysiological recordings of basal ganglia neurons in vivo have confirmed the predicted firing rate changes (albeit inconsistently), but have also revealed disturbed firing patterns at the levels of single cells and larger neuronal networks. For example, dopamine loss in people with idiopathic Parkinson’s disease is associated with the emergence of excessively-synchronized oscillations within and across basal ganglia nuclei.

In this lecture, I will showcase how the use of clinically-relevant animal models of Parkinsonism has provided valuable new insights into the mechanisms underlying these inappropriate neuronal oscillations, with a focus on the cells and circuits of the external globus pallidus (GPe).
I will also highlight how studies of this basal ganglia nucleus in the dopamine-depleted state have advanced our understanding of its operations in health. After correlating the molecular, structural and physiological properties of GPe neurons across models, it is now clear that the GPe contains two major types of neuron that are well suited to perform a division of labor when orchestrating basal ganglia activity and behaviour.

Selected publications

Dodson PD, Dreyer JK, Jennings KA, Syed EC, Wade-Martins R, Cragg SJ, Bolam JP, Magill PJ. (2016) Representation of spontaneous movement by dopaminergic neurons is cell-type selective and disrupted in Parkinsonism. Proc. Natl. Acad. Sci. USA., 113:E2180-88.

 Syed EC, Grima LL, Magill PJ, Bogacz R, Brown P, Walton ME. (2016) Action initiation shapes mesolimbic dopamine encoding of future rewards. Nature Neuroscience 19:34-36.

Dodson PD, Larvin JT, Duffell JM, Garas FN, Doig NM, Kessaris N, Duguid IC, Bogacz R, Butt SJ, Magill PJ (2015) Distinct developmental origins manifest in the specialized encoding of movement by adult neurons of the external globus pallidus. Neuron, 86:501-13.

Abdi A, Mallet N, Mohamed FY, Sharott A, Dodson PD, Nakamura KC, Suri S, Avery SV, Larvin JT, Garas FN, Garas SN, Vinciati F, Morin S, Bezard E, Baufreton J*, Magill PJ*. (2015) Prototypic and arkypallidal neurons in the dopamine-intact external globus pallidus. Journal of Neuroscience, 35:6667-88.

 Nevado-Holgado AJ, Mallet N, Magill PJ*, Bogacz R* (2014) Effective connectivity of the subthalamic nucleus-globus pallidus network during Parkinsonian oscillations. Journal of Physiology, 592:1429-55.

 Mallet N, Micklem BR, Henny P, Brown MT, Williams C, Bolam JP, Nakamura KC, Magill PJ (2012) Dichotomous organization of the external globus pallidus. Neuron, 74:1075-86.

Scientific focus :

Peter Magill is Professor of Neurobiology and Deputy Director of the Medical Research Council Brain Network Dynamics Unit at the University of Oxford. His core research interests lie within the broad fields of movement control and neurodegenerative disorders. He has spent his research career at Oxford elucidating the normal and pathological operational principles of the basal ganglia and partner thalamocortical circuits, with a focus on defining the cellular and systems substrates of impaired behaviours in Parkinsonism.  In vivo electrophysiological recording techniques, quantitative anatomical methods, and the use of genetics-based approaches for the monitoring and manipulation of specified cell types are all central to his research strategy. He currently holds a New Investigator Award from The Wellcome Trust, and is also one of the founding Investigators and Theme Leaders at the Oxford Parkinson's Disease Centre.

Lunch with speaker

If you are interested to share pizzas and a good moment with him (12h30 - 14h), please register on this Doodle..(maximum 15 people, first-come-first-served!)