TY - JOUR T1 - Emergence of Rich-Club Topology and Coordinated Dynamics in Development of Hippocampal Functional Networks <em>In Vitro</em> JF - The Journal of Neuroscience JO - J. Neurosci. SP - 5459 LP - 5470 DO - 10.1523/JNEUROSCI.4259-14.2015 VL - 35 IS - 14 AU - Manuel S. Schroeter AU - Paul Charlesworth AU - Manfred G. Kitzbichler AU - Ole Paulsen AU - Edward T. Bullmore Y1 - 2015/04/08 UR - http://www.jneurosci.org/content/35/14/5459.abstract N2 - Recent studies demonstrated that the anatomical network of the human brain shows a “rich-club” organization. This complex topological feature implies that highly connected regions, hubs of the large-scale brain network, are more densely interconnected with each other than expected by chance. Rich-club nodes were traversed by a majority of short paths between peripheral regions, underlining their potential importance for efficient global exchange of information between functionally specialized areas of the brain. Network hubs have also been described at the microscale of brain connectivity (so-called “hub neurons”). Their role in shaping synchronous dynamics and forming microcircuit wiring during development, however, is not yet fully understood. The present study aimed to investigate the role of hubs during network development, using multi-electrode arrays and functional connectivity analysis during spontaneous multi-unit activity (MUA) of dissociated primary mouse hippocampal neurons. Over the first 4 weeks in vitro, functional connectivity significantly increased in strength, density, and size, with mature networks demonstrating a robust modular and small-world topology. As expected by a “rich-get-richer” growth rule of network evolution, MUA graphs were found to form rich-clubs at an early stage in development (14 DIV). Later on, rich-club nodes were a consistent topological feature of MUA graphs, demonstrating high nodal strength, efficiency, and centrality. Rich-club nodes were also found to be crucial for MUA dynamics. They often served as broker of spontaneous activity flow, confirming that hub nodes and rich-clubs may play an important role in coordinating functional dynamics at the microcircuit level. ER -