Luca Leonardo Bologna

SELF-ORGANIZATION AND NEURONAL AVALANCHES IN NETWORKS OF DISSOCIATED CORTICAL NEURONS

Dissociated cortical neurons from rat embryos cultured onto micro-electrode arrays exhibit characteristic patterns of electrophysiological activity, ranging from isolated spikes in the first days of development to highly synchronized bursts after 3-4 weeks in vitro. In this work we analyzed these features by considering the approach proposed by the self-organized criticality theory: we found that networks of dissociated cortical neurons also generate spontaneous events of spreading activity, previously observed in cortical slices, in the form of neuronal avalanches. Choosing an appropriate time scale of observation to detect such neuronal avalanches, we studied the dynamics by considering the spontaneous activity during acute recordings in mature cultures and following the development of the network. We observed different behaviors, i.e. sub-critical, critical or super-critical distributions of avalanche sizes and durations, depending on both the age and the development of cultures. In order to clarify this variability, neuronal avalanches were correlated with other statistical parameters describing the global activity of the network. Criticality was found in correspondence to medium synchronization among bursts and high ratio between bursting and spiking activity. Then, the action of specific drugs affecting global bursting dynamics (i.e. acetylcholine and bicuculline) was investigated to confirm the correlation between criticality and regulated balance between synchronization and variability in the bursting activity. Finally, a computational model of neuronal network was developed in order to interpret the experimental results and understand which parameters (e.g. connectivity, excitability) influence the distribution of avalanches. In summary, cortical neurons preserve their capability to self-organize in an effective network even when dissociated and cultured in vitro. The distribution of avalanche features seems to be critical in those cultures displaying medium synchronization among bursts and poor random spiking activity, as confirmed by chemical manipulation experiments and modeling studies.