Venue: Bâtiment BBS, amphithéâtre BBS 
Defense in French
Sarah Morceau
INCIA
Team : Decision et adaptation
Thesis supervisor: Mathieu Wolff
Title
Exploit or explore? Neural circuits of learning in volatile environments
Abstract
Taking appropriate decisions in uncertain environments require several critical cognitive processes, including the ability to arbitrate between exploitation (securing a gain by relying on choices associated with a known outcome) and exploration (gaining knowledge on potentially better options) of the environment. My research work has focused on developing an original behavioral task in rats to capture this distinctive feature of human cognition. In an instrumental three-armed bandit task, different levers are associated with optimal and poor outcomes and the most favourable option changes over time within a single session, to prompt animals to navigate between exploitation and exploration strategies. We used this paradigm to examine the role of a thalamocortical circuit defined by projections between the orbitofrontal cortex (OFC) and the mediodorsal thalamus (MD). Broadly speaking, thalamocortical interactions are critical for numerous integrative processes ranging from the perception of environmental stimuli to cognitive functions, as summarized in a review article. We performed post-training excitotoxic lesions of the OFC and the MD and both interventions specifically altered the performance during the exploratory phase. We then used a functional disconnection strategy based on an advanced chemogenetic approach relying on new viral tools to specifically and reversibly inhibit OFC neurons that are directly connected with the MD. This selective perturbation also produced a deficit, demonstrating that inhibiting OFC neurons connecting with the MD is sufficient to impair flexible decision-making in the bandit task, suggesting highly complementary roles for the OFC and the MD. To better understand their respective roles, we sought to understand the dynamics of this thalamocortical circuit when the rat is performing exploitation and exploration phases during a learning session. To do so, we used a calcium imaging technique in freely-moving animals to collect the activity of neuronal populations simultaneously in the OFC and the MD. The initial results highlighted differential activity in the OFC and the MD, demonstrating further functional complementarity, rather than overlap, between cortical and thalamic regions. OFC activity indeed appeared to signal the subsequent choice of the animal and whether a reward was delivered while MD activity also signaled reward omission. Overall, this work indicates that the OFC-MD circuit plays an essential role in decision-making in an uncertain environment. The present findings are highly consistent with work conducted in both human and non-human primates, highlighting thus the translational value of the present approach. Understanding the neural bases of adaptive decision-making represents a major challenge for contemporary neuroscience, and the role of thalamocortical functional connectivity appears to be important for better understanding many mental pathologies.
Key words
Decision, Thalamocortical circuits, Functional neuroanatomy, Fiber photometry, Chemogenetics
Jury
Mr WOLFF Mathieu, Directeur de recherche, CNRS, INCIA, Directeur de thèse
Mme COURTIOL Emmanuelle, Chargée de recherche, CNRS, CRNL, Rapportrice
Mme BENOIT-MARAND Marianne, Maîtresse de conférences, Université de Poitiers, LNEC, Rapportrice
M. BAUFRETON Jérôme, Directeur de recherche, CNRS, IMN, Examinateur
Mme MARIGHETTO Aline, Directrice de recherche, CNRS, Neurocentre Magendie, Université de Bordeaux, Membre invité
Publications
1. Morceau, S., Faugère, A., Coutureau, E., Wolff, M., 2022. The mediodorsal thalamus supports adaptive responding based on stimulus-outcome associations. Current Research in Neurobiology 3, 100057. https://doi.org/10.1016/j.crneur.2022.100057
1. Wolff, M., Morceau, S., Folkard, R., Martin-Cortecero, J., Groh, A., 2021. A thalamic bridge from sensory perception to cognition. Neurosci Biobehav Rev 120, 222–235. https://doi.org/10.1016/j.neubiorev.2020.11.013
1. Morceau, S., Piquet, R., Wolff, M., Parkes, S.L., 2019. Targeting Reciprocally Connected Brain Regions Through CAV-2 Mediated Interventions. Front Mol Neurosci 12, 303. https://doi.org/10.3389/fnmol.2019.00303