Evolution of a complex neuronal network : characterising and influencing the functional connectivity of cultured neurones

Cultures of living cortical neurones, grown in vitro, provide a model of brain function, their longevity plus their openness to experimental manipulation and detailed observation, makes them ideally suited to investigations of micro-scale neural interactions. Functional connectivity between neural units can be defined according to the correlation of their activity, and the functional networks of mature cultured neurones have revealed a complex network organisation. Sharing many properties with other complex networks, such as the Internet, social networks and in vivo brain networks, cultures allow the investigation of how such a network emerges in a biological system. Moreover, they allow one to investigate the influence of experimental manipulation on shaping the network properties. However, very little work compares cultures' complex network properties from different experimental conditions and many questions remain unanswered. The aim of this thesis was to investigate how the functional connectivity of cultured neurones changes under different experimental conditions. A novel toolset and protocol was developed for analysing cultures' functional connectivity within a complex network framework. Spontaneously occurring and experimentally induced changes in connectivity were quantified by comparing topological, spatial and performance properties. Robust results followed from consideration of network topology, size and density influences on the complex network properties. Results confirmed that mature culture's networks are complex, and demonstrated that these emerge from an initially random network organisation to one that supports efficient network-wide flow of information. The influence of electrical stimulation on shaping the network properties is investigated with chronic stimulation during culture development. In conclusion, one can compare complex functional network properties from multiple experimental conditions by applying a reliable link definition, and accounting for differences in network size, density and topology. The present work reveals that the functional networks of cultured neurones spontaneously evolve to a topology optimised for information processing.EThOS - Electronic Theses Online ServiceGBUnited Kingdo