Cortical network function is strongly modulated by the action of GABA interneurons. Understanding the role of different types of interneurons in the generation of network patterns is thus essential. Developmental neurobiology offers both conceptual and experimental tools to address this question. Our research is centred on the integration of GABAergic microcircuits into a functional network during brain development. To describe cortical networks at the scale of microcircuits, we have developed a multidisciplinary approach that combines fast imaging of network dynamics, online data analysis, targeted electrophysiological recordings and histology (Cossart et al. 2005). Doing so, we found a major general step in the maturation of cortical networks. The first electrical network pattern, SPA (Synchronous Plateau Assemblies) emerges at birth and synchronizes electrically coupled neuronal assemblies (Crépel et al., 2007, Allene et al. 2008). We propose that SPAs are a critical step in the maturation of GABAergic microcircuits. More recently, we showed that developing hippocampal networks follow a scale-free topology and demonstrated the existence of functional hubs driving early network oscillations (Bonifazi et al. 2008). These cells are GABAergic neurons characterized by widespread axonal projections. These two findings provide the experimental foundation and conceptual framework for this project. We will address three objectives. First, we will perform a functional characterization of hub neurons orchestrating synchrony in developing cortical networks in vitro and in vivo. Second, we will address the role of SPA in the maturation GABAergic microcircuits. Last, we will examine circuit disorders related to developmental GABA Interneuropathies .
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Funding SchemeERC-SG - ERC Starting Grant
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