PATHOPHYSIOLOGY OF SYNAPTIC TRANSMISSION
Department: Neuroscience
Research subject
The synapse is the structural entity allowing the communication between neurons in our brain. Understanding the functioning of the synapse will soon enable to discover new therapeutic strategies to treat neurologic and psychiatric disorders. This objective might be one of the more ambitious and exciting challenges in science for the XXI century!
Our research investigations are designed to identify the best therapeutic targets. We are studying the molecular and cellular determinants involved in synapses formation, synaptic transmission and plasticity and functional neuronal networks sustaining cognitive behaviors adapted to our environment. A translational research enables a better understanding of molecular and cellular deficiencies triggering behavioral disorders. In particular, we are investigating two major public health concerns: autism spectrum disorders and behavioral disorders induced by general anesthetic agents. Our attention is focused on the identification of synaptic proteins involved in glutamate receptors’ subcellular trafficking, organization at the synapse, and signaling. Our previous work has demonstrated that the different functions of a receptor are based on its ability to engage in specific protein-protein interactions with scaffolding proteins and effectors to form a functional unit called a receptosome. These protein interactions are finely regulated, in a very dynamic way, by surrounding stimuli. Understanding 1) whether a receptor is activated as free molecule or part of different complexes and 2) its role in each of these conditions are essential biological issues that offer the possibility of exclusively targeting the altered signaling pathway in a given pathology.
Our projects are structured according to 3 main axes
- Develop technologies for the study of protein-protein interaction dynamics and neuronal signaling
- Constraining molecular dynamics at the synapses to understand their physiological relevance in cellular plasticity and cognitive performance.
- Take advantage of mouse models: towards translational research, from mouse to patient.
Team
Major publications
- Sebastianutto* I, Goyet* E, Laura Andreoli+, Joan Font-Ingles+, David Moreno-Delgado+, Nathalie Bouquier, Céline Jahannault-Talignani, Enora Moutin, Luisa Di Menna, Natallia Maslava, Jean-Philippe Pin, Laurent Fagni, Ferdinando Nicoletti, Fabrice Ango, Cenci# A and Perroy# J. D1 and mGlu5 form functional heteromers mediating non-canonical dopamine signaling in Parkinson’s disease – Journal of Clinical Investigation - in press
- Sola C, Menacé C, Bringuier S, Saour AC, Raux O, Mathieu O, Capdevila X and Dadure C. Transversus Abdominal Plane Block in Children: Efficacy and Safety: A Randomized Clinical Study and Pharmacokinetic Profile. Anesth Analg. 2019 Jun;128(6):1234-1241.
- Dussaux C, Szabob V, Chastagnier Y, Fodor J, Léger JF, Bourdieu L, Perroy J and Ventalon C - Fast confocal fluorescence imaging in freely behaving mice. Sci. Reports – 2018 Nov 2;8(1):16262
- Goyet E., Bouquier N., Ollendorff V. and Perroy J. Fast and high resolution single-cell BRET imaging. Sci. Reports - 2016 Jun 15;6:28231
- Guo, W., Ceolin, L., Collins, K. A., Perroy, J. and Huber, K. M. Elevated CaMKIIalpha and Hyperphosphorylation of Homer Mediate Circuit Dysfunction in a Fragile X Syndrome Mouse Model. Cell reports 2015 13, 2297-2311