Venue : Centre Broca Nouvelle-Aquitaine
Patricia Bonnavion
Université Libre de Bruxelles, Belgium
Website : https://neurophylab.ulb.be/patricia-bonnavion
Invited by Jérôme Baufreton
Title
The dark side of dopamine: the paradoxical influences of dopamine on striatal motor functions
Abstract
The initial description of dopamine’s actions in the brain highlighted its importance in promoting movement and mediating pleasure and reward, but its role is much more versatile, with unexpected effects that are sometimes even opposed to these original major functions. The heterogeneity of the mesencephalic dopaminergic system is now evident, mainly characterized by the existence of multiple sub-circuits involving sub-populations of dopamine neurons targeting distinct structures to explain such contradictory influences, such as aversion, or motor inhibition, which was the focus of my work. This multi-faceted influence of dopamine is not only exerted through these parallel circuits, but also varies according to the animal’s status and context, and through complex signaling on its targets. I will present some findings revealing an antagonistic mode of action of dopamine that can restore a motor brake, upon certain conditions, involving unconventional targets in the striatum necessary for the proper control of movement.
The action of dopamine in the striatum is often postulated to promote movement through a synergistic effect on activatory D1 and inhibitory D2 receptors, so far thought to be exclusively expressed in the two classical direct and indirect pathways, respectively. One of the main findings of our studies was the identification of a third pathway, originating from “hybrid” neurons, previously described by the co-expression of D1 and D2 receptors, playing a key role in balancing the motor functions of the two main striatal pathways, and in mediating paradoxical actions of dopamine in the basal ganglia system.
Biosketch
Patricia Bonnavion is an FNRS group leader at the Neurophysiology lab of the Université Libre de Bruxelles (ULB). She studied Sleep Physiology and Neuroanatomy at the Université Sorbonne Paris 6, and obtained her PhD in Physiology and Pathophysiology at the INSERM Neuropsychopharmacology unit directed by Prof. Michel Hamon, under the supervision of Dr Joëlle Adrien. Her PhD work focused on brainstem serotonergic neurotransmission in the regulation of vigilance states, highlighting the functional heterogeneity of the raphe serotonergic system and identifying a novel ponto-hypothalamic circuit mediating serotonergic regulation of sleep/wake cycles in rodents.
She joined Prof. Luis de Lecea’s group at Stanford University for her postdoc, interrogating monoaminergic and peptidergic interactions in the hypothalamus in the control of arousal and stress, using optogenetic tools to control and monitor neuronal activities in freely behaving mice.
She then returned to Europe, joining the Neurophysiology lab at ULB in Belgium as a research associate with the team of Dr. Alban de Kerchove, to tackle monoaminergic functions in a more complex integrative center, namely the striatum, first deconstructing the striatum’s modus operandi under the influence of dopamine in motor control. She has recently launched her own team as an FNRS Principal Investigator, returning to sleep questions focusing on the influence and role(s) of the striatum and its interplay with dopamine during sleep.
Publications
Unexpected contributions of striatal projection neurons coexpressing dopamine D1 and D2 receptors in balancing motor control.
Bonnavion P., Varin C., Fakhfouri G., De Groote A., Cornil A., et al. Nature Neuroscience, 2024 in press. BioRXiV: DOI: https://doi.org/10.1101/2022.04.05.487163
The respective activation and silencing of striatal direct and indirect pathway neurons support behavior encoding.
Varin C., Cornil A., Houtteman D., Bonnavion P., de Kerchove d’Exaerde A. Nature Communication, 14 (1): 4982.
DOI: 10.1038/s41467-023-40677-0
The GABAergic Gudden’s dorsal tegmental nucleus: a new relay for serotonergic regulation of sleep-wake behavior in the mouse.
Chazalon M., Dumas S., Bernard J.-F., Sahly I., Tronche F., deKerchove d’Exaerde A., Hamon M., Adrien J., Fabre V.*, Bonnavion P.* Neuropharmarcology, 138:315-30, 2018.
DOI: 10.1016/j.neuropharm.2018.06.014
Hypothalamic Tuberomammillary Nucleus Neurons: Electrophysiological Diversity and Essential Role in Arousal Stability.
Fujita A.*, Bonnavion P.*#, Wilson M.H., Mickelsen L.E., Bloit J., de Lecea L., Jackson A.C#. Journal of Neuroscience, 37: 9574-92, 2017.
DOI: 10.1523/JNEUROSCI.0580-17.2017
Antagonistic interplay between hypocretin and leptin in the lateral hypothalamus regulates stress responses.
Bonnavion P., Jackson A.C., Carter M.C., de Lecea L. Nature Communication. 6: 6266, 2015.
DOI: 10.1038/ncomms7266