Cortico-pallidal circuits and executive functions: optogenetic, fiber photometry and behavioral studies in mice

The NeuroSchool PhD Program of Aix-Marseille University (France) has launched its annual calls for PhD contracts for students with a master's degree in a non-French university. 

This project is one of the proposed projects. Not all proposed projects will be funded, check our website for details.

The external globus pallidus (GPe) is an integral component of the basal ganglia, a highly organized network of subcortical nuclei that form with frontal cortex and the thalamo-cortical system several distinct but partly overlapping loops that control many facets of voluntary motor behaviour. The GPe has long been regarded as a simple relay within the BG, connecting the striatum and the subthalamic nucleus in the indirect pathway. In the past years, a diversity of GABAergic cell types and anatomical connectivities of GPe were uncovered suggesting that it may rather act as an integrative hub for shaping motor and non-motor aspects of behavior. More recently, direct projections from the neocortex to GPe were uncovered, indicating that this nuclei provides an entry for cortical information to the BG. Despite surge of interest over the past years, our understanding of the functional significance of the cellular diversity and anatomical connectivity of GPe remains largely incomplete.  The aim of this project is to specify the nature of the functional relationship between the cortex and GPe. We will use a multidisciplinary approach combining original optogenetic tools with calcium imaging and behavioral techniques (e.g., motor skill learning, fear conditioning and operant conditioning tasks) to selectively manipulate cortico-pallidal projections and GPe neurons in mice and clarify their contribution to cognitive, emotional and motor functions subserved by BG. Transgenic mice (FoxP2-cre and Parvalbumin (PV)-cre) will be used to specifically target FoxP2-expressing and PV-expressing neurons, which represent two distinct populations of GPe projection neurons. Dual-color optogenetic studies with blue and red lights will be used to manipulate conjointly the activity of cortical projections and GPe output neurons and determine how topdown cortical control of GPe takes place to support implementation of flexible, goal-directed behavior. Photometric calcium recordings will be conducted in parallel to monitor changes of postsynaptic cortico-pallidal transmission. As well as enhancing our understanding of how cortico-pallidal circuits contribute to implementation of adaptive goal directed behavior. This project will also provide new grounds that may guide development of more effective and well-tailored DBS treatments for psychiatric disorders.   This project will be conducted in the team “Cognition and Pathophysiology of Basal Ganglia” headed by Drs. AM. Ouagazzal & P. Gubellini. The research team has broad-based expertise that spans neuropharmacology, biochemistry, in vivo optogenetic/calcium imaging, behavioral genetics and patch-clamp electrophysiology. During his (her) PhD work, the student will acquire strong expertise in behavioral analysis (battery of test for cognitive, emotional and motor functions) optogenetic and fiber photometry. He/she will also acquire immunofluorescence techniques to map protein expression and brain circuitry. The student will benefit from a rich scientific and technical environment, in the CRPN, that will let him develop his/her researcher potential and communication skills. 

Within Aix Marseille Université, NeuroMarseille brings together 8 research laboratories and NeuroSchool, a graduate school in neuroscience, to increase the attractiveness of the university, international collaborations, interdisciplinarity, links with the clinical and industrial worlds and the integration of students into professional life. 

Launched in July 2018, NeuroSchool unifies and harmonizes the training of the third year of the Bachelor of Life Sciences (Neuroscience track), the Master's and the PhD in Neuroscience. 

• Expected candidate profile : Knowledge in optogenetic or fiber photometry, immunochemistry, Matlab or python programming