Lieu : centre Broca
Title
Network dynamics of Basal Ganglia circuits in function and dysfunction
Abstract
This ‘Habilitation à Diriger des Recherches’ (HDR) presents an overview of my contributions to advancing our understanding of the network dynamics in basal ganglia (BG) circuits and their essential role in both normal motor functions and pathological conditions, such as those observed in Parkinson’s disease (PD) or levodopa-induced dyskinesias (LIDs). Through an integrated approach combining in vivo electrophysiology, cell-type specific optogenetic manipulations, and fine motor behavioral testing in rodent models, my research has elucidated key neuronal mechanisms that underlie both BG function and dysfunction. Specifically, my past work has revealed the key role of the external globus pallidus (GP) in orchestrating abnormal synchronized beta oscillations in PD, highlighted the critical influence of Arky-GP neurons in action inhibition, and identified novel principle of functional connectivity that govern BG network dynamics. Together, these findings support a refined view of BG circuit organization, where cellular diversity is intrinsically linked to behavioural specialization, whether in the execution or suppression of goal-directed actions.
This HDR also details how my earlier research has progressed into two major ongoing projects: the MOTOR-Code project, which further investigates the cellular and network mechanisms driving beta oscillation generation and their impact on motor function; and the MOTOR-Gate project, which explores the causal involvement of Arky-GP neurons in both normal or abnormal (i.e. LIDs) movement generation. Together, these projects enhance our understanding of the anatomo-functional organization of basal ganglia circuits, particularly their role in motor control, with the potential to inform future therapeutic strategies for motor disorders like Parkinson’s disease and LIDs.
Key words
Basal Ganglia, Motor control, Parkinson’s disease, Levodopa-induced dyskinesias, Normal and Abnormal Network Dynamics
Selected publications
Guilhemsang L, Mallet NP (2024) Arky-GP neurons in basal ganglia circuits: Unveiling novel pallidostriatal loops. Current Opinion in Neurobiology Nov 27:84:102814.
Aristieta A, Barresi M, Lindi S, Barriere G, Courtand G, de la Crompe B, Guilhemsang L, Gauthier L, Fioramonti S, Baufreton J, Mallet NP. (2021) A disynaptic circuit in the globus pallidus controls locomotion inhibition. Current Biology, 22;31(4):707-721.e7.
de la Crompe B, Aristieta A, Leblois A, Elsherbiny S, Boraud T, Mallet NP. (2020) The globus pallidus orchestrates abnormal network dynamics in a model of Parkinsonism. Nature Communications 26;11(1):1570.
Mallet N, Schmidt R, Leventhal D, Chen F, Amer N, Boraud T, and Berke JD (2016) Arky-GP cells send a stop signal to striatum. Neuron (89:308-316).
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 21:1075-86.