Experimental and modeling study of extracellular electrical stimulation of neural networks using microelectrode arrays >>> Why studying extracellular electrical stimulation? Using extracellular electrical stimulations of the central nervous system (CNS) is currently a major stake in Neuroscience, both in fundamental and clinical research. In clinical research, these stimulations are –or will be– used with therapeutic aims, in order to restore injured motor or sensorial functions [injured spinal cord stimulation, deep brain stimulation, cochlear or retinal implants, and brain-machine interfaces]. In fundamental research, this type of stimulation is used to investigate networks, for instance to bring to light their organization, connectivity, and to study their responses to exogenous stimulations, or even induce plasticity phenomena. To study extended networks (several mm), disposing of a high number of recording and stimulation sites is crucial. For that purpose, MicroElectrode Arrays (MEAs) including tens of recording and stimulation sites have been developed for about 20 years, in order to study these networks in a bidirectional way, with a recording/stimulation approach. An important criterion to characterize the efficiency of an extracellular simulation is its ability to excite selectively a target area in a nervous tissue. For instance, to realize retinal implants with a sufficient spatial resolution, we need to be able to excite small groups (some tens) of ganglion cells (in the case of epiretinal implants) or horizontal cells (for subretinal implants). For such implants, it is essential to stimulate the tissue very focally, to achieve "stimulation pixels". For other applications, the target structures can be larger, of the order of the cm (for instance, in the case of Deep Brain Stimulation, where the target structure is the subthalamic nucleus), but even in such cases, stimulations must be well controlled spatially to optimize their effects. Despite this need of spatial control, the extents of tissue activated by different types of stimulations remain partially known, in particular for distances above several hundreds of microns. Moreover, the mechanisms underlying the excitation of neural cells by an extracellular stimulation are still poorly understood. >>> The aim of my PhD thesis was to achieve a global understanding of the mechanisms of the extracellular electrical stimulation, and to develop a new stimulation strategy allowing focal stimulations with MEAs, independent of the type of tissue, especially independent of the orientation and dimensions of target neurons. >>> For that purpose, we combined experimental and modeling approaches. Experimentally, using a whole preparation of mouse embryo spinal cord laying on a MEA, we showed that monopolar stimulations are not focal. To understand the stimulation mechanisms and improve the spatial selectivity of the stimulations, we developed a modeling approach which led us to: 1) validate a realistic model for the calculation of the potential field generated by the electrodes, based on an explicit modeling of the interface impedance between the metallic electrode and the tissue; 2) derive a theoretical estimation of the membrane potential of neurons excited by such fields. Finally, we invented and patented a new electrode configuration to increase the focality of monopolar stimulations. >>> A long-term goal is to use these results to study the impact of exogeneous electrical activities on the maturation of neural networks during ontogenesis. More generally, improving the focality of extracellular stimulations, using for instance the new electrode configuration, will allow to stimulate neural networks with an increased spatial control, and to overcome the current limitations of some neural implants. |
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PhD |