Hubs in Epilepsy · Functional connectivity and the role of hub neurons in epilepsy

Determining the functional structure of neuronal networks has become an increasingly important tool to link functional and anatomical network structure. Recently, the analysis of functional network structure in the developing rodent hippocampus revealed the presence of highly connected, functional “hub neurons” with the ability to greatly influence synchronous network activity. Additionally, these developmental hub neurons were shown to be early born neurons with an impressive anatomical structure which is conserved in adulthood. Furthermore, computational modeling has predicted the importance of anatomical hub neurons in the development of synchronous epileptiform activity. Here, we therefore propose to study the relationship between functional and anatomical network structure in a chronic model of temporal lobe epilepsy in order to link changes in network structure with the development of synchronous epileptiform neuronal dynamics. Specifically, we plan to use multi-beam two-photon imaging to study acute slices under healthy and pathological conditions using the pilocarpine mouse model of temporal lobe epilepsy. To achieve this goal, we propose two complimentary methods to determine the role of network structure and hub neurons in the development of pathological neuronal activity: 1) The construction and analysis of functional network structure from imaged calcium dynamics of the dentate gyrus in both healthy and pathological tissue, and 2) The direct observation of the impact of developmental hub neurons on network dynamics in epileptic tissue obtained from transgenic mice whose early born hub neurons have been labeled with GFP.