Thesis defense – Florence Pontais

Venue: BBS

Florence Pontais
Team: DECAD, INCIA

Surpervisor: Catherine Le Moine

Title

Neural substrates of risk-based decision-making. Contribution of the orbitofrontal cortex subregions in rats and study of inter-individual variability in risk-taking choice behaviors

Abstract

Risk-based decision-making involves choosing between alternatives whose outcomes occur with known probabilities. Common to both humans and animals, this cognitive process underlies both economic decisions and foraging. In these situations, choosing the option with the greater potential reward usually comes with a cost, such as the risk of getting nothing at all. Making an optimal decision then requires assessing risks and benefits and their associated probabilities to estimate the expected value of each option. Crucially, when the probabilities change, learning to re-evaluate the options and adjust choices accordingly becomes necessary. This ability is impaired in several neuropsychiatric disorders, particularly addictive behaviors.

Understanding how these choices develop during learning, and the underlying neural substrates, thus represents a major challenge. The orbitofrontal cortex (OFC) is a key region for behavioral flexibility as well as value- and uncertainty-based decision-making. Functionally heterogeneous, the OFC includes several subregions whose contributions to these processes are distinct. However, the role of its medial (mOFC) and ventrolateral (vlOFC) parts in risk-based decision-making remains poorly understood. This thesis combines behavioral, lesion-based, chemogenetic, and fiber photometry approaches in rats in order to better understand the role of these subregions in the learning of risk-based decision-making.

We developed a probabilistic task in which rats choose between an option associated with a modest but certain reward and a risky option that can yield either a larger reward or no reward at all. The reward probability varies within the session and defines the risky option as advantageous or disadvantageous, requiring the rats to adjust their choices. Well-trained rats adapt their choices to each probability, but their learning dynamics differ between probabilities. Pre-training lesions of the mOFC and vlOFC showed that only vlOFC lesions increased choice latencies at the beginning of learning, without impacting choices themselves. In a second experiment, chemogenetic inactivation of the vlOFC specifically at the beginning of learning reduced risky choices and altered choice strategies until the end of learning. In parallel, photometry recordings revealed that vlOFC activity during choices is modulated by reward value. Finally, inter-individual differences were observed across learning. Males and females differed in their choice strategies and response latencies. Furthermore, a meta-analysis revealed rats with extreme profiles (risk-seeking or risk-averse), which we characterized using multivariate analyses.

In conclusion, this work highlights the specific involvement of the vlOFC in learning to make decisions under risk, when re-evaluating options and adapting choices to a change in risk are required. Moreover, it shows that decision-making phenotypes and sex-related differences emerge and are characterized during the learning process.

Keywords: risk-based decision-making, learning, orbitofrontal cortex, probabilistic discounting task,
inter-individual differences

Jury

Mme COURTIOL Emmanuelle CR, CRNL, UCBL, Lyon – Rapportrice
M. FAURE Philippe DR, ESPCI, Université PSL, Paris – Rapporteur
Mme GRANON Sylvie PU, NeuroPSI, Université Paris-Saclay, Paris – Examinatrice
M. BORAUD Thomas DR, IMN, Université de Bordeaux – Examinateur
Mme LE MOINE Catherine DR, INCIA, Université de Bordeaux – Directrice de thèse

• Place
  BBS
  
• Dates
  On 29 October 2026 at 14:00