Venue: INCIA – Zone nord Bat 2 2ème étage – salle de réunion
Cortex préfrontal et flexibilité comportementale : implication de la noradrénaline
Juan Carlos Cerpa
INCIA
Thesis supervisor: Etienne Coutureau
Defense in french
Abstract
An organism depends for its survival on the ability to take adaptive decisions in an ever-changing environment. These decisions involve several cognitive processes that can be revealed by the study of associative learning processes. Thus, action control has been found to rely on processes that distribute across a network of cerebral structures including prefrontal regions. Prefrontal functions are largely influenced by neuromodulators such as noradrenaline, which is thought to be involved in behavioural flexibility. My Ph.D. project therefore aimed at clarifying the role of noradrenergic modulation of prefrontal cortex regions in adapting a subject’s behaviour to changes in action consequences. In the first chapter, we studied the organization of noradrenergic innervation in the various prefrontal areas, by means of an automated quantification method. In the second chapter, we applied a behavioural protocol requiring flexible learning of the causal relationships between actions and their outcomes. Using this protocol and neurotoxins to deplete prefrontal regions from noradrenergic innervation, we showed that noradrenaline in a specific area, the orbitofrontal cortex, was necessary to action control, in particular to mediate changes in the identity and value of expected outcomes. Comparing this contribution to the role of medial prefrontal cortex on one hand, and of dopaminergic modulation on the other hand, suggests that the role of noradrenergic neuromodulation is both region- and mediator-specific. In the third chapter, we developed a series of chemogenetic approaches to identify the temporal involvement of noradrenaline in the various phases of the task, and we identified some of the limits of these approaches. This work confirms the importance of neuromodulation in prefrontal cortical function and furthers our understanding of cerebral circuits involved in action control and adaptation to a changing environment.
Keywords : Prefrontal cortex ; Orbitofrontal cortex ; Noradrenaline ; Locus Cœruleus ; Action ; Adaptation ; Instrumental learning ; Rat
Publications
Cerpa JC, Marchand A.R*, Coutureau E* – Distinct Regional Patterns in Noradrenergic Innervation of the Rat Prefrontal Cortex, Journal of Chemical Neuroanatomy (2019), https://doi.org/10.1016/j.jchemneu.2019.01.002
Parkes S.L, Ravassard P.M, Cerpa JC, Wolff M, Ferreira G, Coutureau E – Insular and Ventrolateral Orbitofrontal Cortices Differentially Contribute to Goal-Directed Behavior in Rodents. Cerebral Cortex, 2018 1-13. doi: 10.1093/cercor/bhx132
Cerpa JC, Marchand A.R, Salafranque Y, Pape J-R, Kremer E.J, Coutureau E – Targeting catecholaminergic systems in transgenic rats with a CAV-2 vector harbouring a Cre-dependent DREADD cassette (soumis)
Cerpa JC, Parkes S.L, Dehove M, Faugère A, Wolff A, Marchand A.R, Coutureau E – Noradrenergic control of action-outcome identity reversal in the orbitofrontal cortex (en préparation)
Jury
M. Etienne COUTUREAU – CNRS – Université de Bordeaux – Directeur de thèse
M. Sébastien BOURET – CNRS – Institut du Cerveau et de la Moelle épinière – Rapporteur
Mme Nicole EL MASSIOUI – CNRS – Université Paris-Saclay – Rapporteur
Mme Sylvie GRANON – Université Paris-Saclay – Examinateur
M. Jean-Louis GUILLOU – Université de Bordeaux – Examinateur
Mme Karine GUILLEM – CNRS – Université de Bordeaux – Examinateur