Thesis defense – Emma Marillat

Venue: BBS

Soutenance en français

Emma Marillat

Supervisors: Mathieu Wolff (INCIA) and Frédéric Gambino (IINS)

Title

Thalamocortical base of decision making in uncertain environments

Abstract

Decision-making in uncertain environments relies on a dynamic balance between exploring new options and exploiting choices already known to be advantageous. Understanding the neural substrates of this balance is a major challenge in cognitive neuroscience. The orbitofrontal cortex (OFC) and the mediodorsal thalamic nucleus (MD) appear to be key players in adaptive decision-making, but the functional interactions between these regions remain poorly characterized.

To investigate this question, we used a “three-armed bandit” instrumental task in which the most favorable option (one lever among three) varies over time, forcing animals to alternate between exploration and exploitation strategies. We first established that lesioning the OFC or the MD produces a specific deficit in this task, reflected as a difficulty in recovering optimal performance when the most favorable option is switched. Importantly, we also established that lesioning the submedius thalamus, the other major thalamic afferent to the OFC, has no effect. In addition, a viral neuroanatomical tracing strategy allowed us to establish that although the thalamocortical pathways originating from the MD and the Sub both converge onto the OFC, they predominantly contact different cortical neuronal populations. Taken together, these data suggest the existence of two anatomically and functionally distinct thalamocortical circuits within the OFC.

To further clarify the functional role of the OFC-MD circuit, we then assessed the functional contribution of each region using a fiber photometry approach in animals performing the task. We observed that OFC activity increases both at the time of choice and when a reward is obtained, indicating that the choice and its reinforcement appear to be represented at the cortical level. In contrast, thalamic activity is modulated neither by the choice nor by the reward, as the MD shows increased activity only when the animal evaluates the consequences of its choice. Interestingly, this thalamic activation appears to result from learning, since the MD is essentially silent in naive animals. This dynamic thus suggests that the MD does not directly encode reward value, but rather contributes to the maintenance and consolidation of optimal choice strategies by potentially influencing prefrontal regions at the moment when the current value representation of the choice may be called into question. Taken together, these data indicate a distinct and complementary specific functional contribution of the OFC and the MD, ensuring the implementation of adaptive strategies when an abrupt change occurs in the environment.

These results obtained in rodents converge with earlier work conducted in human and non-human primates, suggesting broad conservation of the functional organizational principles of thalamocortical circuits across the phylum. Alterations in thalamocortical connectivity are a recurrent symptom in numerous psychiatric disorders, such as addictive disorders, schizophrenia, or obsessive-compulsive disorder. Better understanding the functional organizational principles of thalamocortical circuits could therefore pave the way toward improved management of the alterations in behavioral flexibility and decision-making seen in these mental disorders.

Key-words: Decision, Adaptative behavior, Thalamocortical circuits, Chemogenetic, Fiber photometry

Jury

• Emmanuelle Courtiol, CR (Université de Lyon) : rapporteure
• Romain Goutagny, DR (Université de Strasbourg) : rapporteur
• Agnès Nadjar, Pr (Université de Bordeaux) : examinatrice
• Mathieu Wolff, DR (Université de Bordeaux) : directeur de thèse
• Frédéric Gambino, CR (Université de Bordeaux): codirecteur de thèse

• Place
  BBS
  
• Dates
  On 21 October 2026 at 14:00