Venue : Centre Broca
Léa Bonamy
Team : Dopamine and neuronal assemblies
IMN
Title
Role of arkypallidal neurons in the motor symptoms of Parkinson’s disease and L-DOPA-induced-dyskinesia : study in a rodent model
Abstract
The external Globus Pallidus (GPe) is a central hub within the basal ganglia, mainly involved in relaying information through the indirect pathway. It consists primarily of GABAergic neurons, divided into prototypic and arkypallidal (ARKY) subtypes, distinguished by molecular and electrophysiological signatures. Our team recently showed that optogenetic activation of ARKY neurons suppresses ongoing action, suggesting a key role in movement control. Parkinson’s disease (PD), the second most common neurodegenerative disorder worldwide, is characterized by severe motor impairments. While dopamine replacement therapy with L-DOPA initially alleviates symptoms, its long-term use often results in involuntary movements known as L-DOPA-induced dyskinesias (LIDs). Despite extensive research on PD and LIDs, the role of ARKY neurons in these conditions remains poorly understood. Therefore, the objective of my PhD has been to investigate functional modifications of ARKY neurons in mice models of PD and LID using multidisciplinary approaches. My work revealed that ARKY neuron’s activity is altered in PD and LID behaving mice. I demonstrated that ARKY intrinsic excitability is modified in PD and LID and that ARKY neurons projections to the striatum are enhanced in both pathophysiological conditions. Furthermore, I showed that ARKY neurons are inhibited by L-DOPA in acute brain slices suggesting that L-DOPA exerts its dyskinetic effects partly by acting in the GPe.
Publications
Marques A, Beze S, Lambert C, Bonamy L, de Chazeron I, Rieu I, Chiambaretta F, Durif F. Psycho-sensory modalities of visual hallucinations and illusions in Parkinson’s disease. Rev Neurol (Paris). 2021 Dec;177(10):1228-1236. doi: 10.1016/j.neurol.2021.04.007. Epub 2021 Jul 5. PMID: 34238577.
Glangetas C, Guillaumin A, Ladevèze E, Braine A, Gauthier M, Bonamy L, Doudnikoff E, Dhellemmes T, Landry M, Bézard E, Caille S, Taupignon A, Baufreton J, Georges F. A population of Insula neurons encodes for social preference only after acute social isolation in mice. Nat Commun. 2024 Aug 21;15(1):7142. doi: 10.1038/s41467-024-51389-4. PMID: 39164260; PMCID: PMC11336167.
Lebouc M, Bonamy L, Dhellemmes T, Scharnholz J, Richard Q, Courtand G, Brochard A, Martins F, Landry M, Baufreton J, Garret M. Developmental alterations of indirect-pathway medium spiny neurons in mouse models of Huntington’s disease. Neurobiol Dis. 2025 May;208:106874. doi: 10.1016/j.nbd.2025.106874. Epub 2025 Mar 14. PMID: 40090469.
Jury
Rapportrice : Daniela Popa
Rapporteur : Abdel-Mouttalib Ouagazzal
Examinatrice : Patricia Bonnavion
Examinatrice et Présidente du jury : Catherine Le Moine
Invité : Dominique Guehl
Directeur de Thèse : Jérôme Baufreton