Functional organization and networ resilience in self-organizing clustered neuronal cultures
[eng] Major dynamical traits of a neuronal network are shaped by its underlying circuitry. In several neurological disorders, the deterioration of brain's functionality and cognition has been ascribed to changes in the topological properties of the brain's circuits. To deepen in the unders...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/102591 |
| Acceso en línea: | https://hdl.handle.net/2445/102591 http://hdl.handle.net/10803/396114 |
| Access Level: | acceso abierto |
| Palabra clave: | Xarxes neuronals (Neurobiologia) Neurones Cultius (Biologia) Neural networks (Neurobiology) Neurons Cultures (Biology) |
| Sumario: | [eng] Major dynamical traits of a neuronal network are shaped by its underlying circuitry. In several neurological disorders, the deterioration of brain's functionality and cognition has been ascribed to changes in the topological properties of the brain's circuits. To deepen in the understanding of the activity-connectivity relationship, neuronal cultures have emerged as remarkable systems given their accessibility and easy manipulation. A particularly appealing configuration of these in vitro systems consists in an assembly of interconnected aggregates of neurons termed 'clustered neuronal networks'. These networks exhibit a complex dynamics in which clusters fire in small groups, shaping communities with rich spatiotemporal properties. The detailed characterization of this dynamics, as well as its resilience to perturbations, has been the main objective of this thesis. In our experiments we monitored spontaneous activity using calcium fluorescence imaging, which allows the detection of neuronal firing events with both high temporal and spatial resolution. The detailed analysis of the recorded activity, in the context of network theory and community analysis, allowed for the quantification of important properties, including the effective connectivity map and its major topological descriptors. As major results, we observed that these clustered networks present hierarchical modularity, assortative mixing and the presence of a rich club core, a series of features that have also been observed at the scale of the brain. All these characteristic topological traits are associated with a robust architecture that reinforces and stabilizes network activity. To verify the existence of such robustness in our cultures, we studied their resilience upon chemical and physical damage. We concluded that, indeed, clustered networks present higher resilience compared to other configurations. Moreover, these clustered networks exhibited recovery mechanisms that can be linked to the balance between integration and segregation in the network, which ultimately tend to preserve network activity upon damage. Thus, these in vitro preparations offer a unique scenario to explore vulnerability in networks with topological properties similar to the brain. Moreover, the combination of all these approaches can help to develop models to quantify damage upon network degradation, with promising applications for the study of neurological disorders in vitro. |
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