ED Sciences de la Vie et de la Santé
Regulation of motor behaviors under physiological and pathophysiological conditions by the pedunculopontine nucleus
by Abderrahman FETTAH (Institut de neurosciences cognitives et intégratives d'Aquitaine)
The defense will take place at 14h00 - Amphi Centre Broca Nouvelle - Aquitaine Centre Broca Nouvelle-Aquitaine - rez de chaussée 146 rue Léo Saignat - CS 61292 - Case 28 33076 Bordeaux cedex
in front of the jury composed of
- Grégory BARRIERE - Chargé de recherche - CNRS-Université de Bordeaux - Directeur de these
- Véronique COIZET - Chargée de recherche - Grenoble Institut des Neuroscience, Inserm U1216 - Rapporteur
- Marianne BENOîT MARAND - Professeure des universités - Université de Poitiers, LNEC Inserm U1084 - Rapporteur
- Claire WYART - Directrice de recherche - Institut du Cerveau, Sorbonne Université - Examinateur
- Dominique GUEHL - Professeur des universités - praticien hospitalier - Université de Bordeaux, CNRS, IMN, UMR 5293 - Examinateur
The recent identification of specialized motor modules in the brainstem that regulate various behaviors (locomotion and fine movements, etc.) has prompted a reexamination of the organization and functionality of motor circuits. In this project, conducted in mice, we aim to investigate the role of the pedunculopontine nucleus (PPN) in motor control. This study is motivated by the PPN's position at the junction between the basal ganglia, which provide input to the PPN, and the motor regions of the brainstem, to which it sends projections. Our primary objective is to map the afferent and efferent connections of the PPN using anatomical tracers injected through stereotaxic techniques. The secondary objective is to functionally characterize the role of glutamatergic neurons of the PPN during various motor behaviors (locomotion, food & water intake, and object manipulation) by employing bilateral recordings of neuronal activity through techniques such as in vivo calcium imaging, fiber photometry, and mini-endoscopy under normal conditions as well as after inducing a Parkinsonian syndrome. The final goal is to establish a causal link between PPN activity and the expression of motor behaviors via optogenetic manipulation of PPN glutamatergic neurons. Preliminary results, which will require validation, suggest that the activity of PPN glutamatergic neurons influences all examined behaviors in both physiological and pathological contexts. Furthermore, this activity appears to be modified during the progression of Parkinsonian syndrome and the onset of L-DOPA-induced dyskinesia.
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
by Florence PONTAIS (Institut de neurosciences cognitives et intégratives d'Aquitaine)
The defense will take place at 14h00 - Amphithéâtre BBS Bâtiment Bordeaux Biologie Santé 2 Rue Dr Hoffmann Martinot, 33000 Bordeaux
in front of the jury composed of
- Catherine LE MOINE - Directrice de recherche - Université de Bordeaux - Directeur de these
- Emmanuelle COURTIOL - Chargée de recherche - Centre de Recherche en Neurosciences de Lyon (CRNL) - Rapporteur
- Phillippe FAURE - Directeur de recherche - École supérieure de physique et de chimie industrielles (ESPCI)- Université Paris Sciences et Lettres (PSL) - Rapporteur
- Sylvie GRANON - Professeure des universités - Insitut de Neuroscience Paris Saclay (NeuroPSI) - Examinateur
- Thomas BORAUD - Directeur de recherche - Université de Bordeaux - Examinateur
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 the 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 have 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.