Oscillatory activity synchronized over a large population of neurons is the signature of the developing brain and play a major role in the construction of neuronal circuits. The hypothesis at the basis of our research proposal is that the initiation of synchronous network events is dependent on precise connectivity patterns of the neuronal network. Models of complex systems and networks offer solid tools to characterize mathematically the dynamics of neural circuits and predict the existence of networks “hubs”, i.e. neurons with spread and much larger number of connections, which strongly influence the state of the network. The aim of the present project is to identify specific types of neurons driving the oscillatory activity in the hippocampus during development. In order to find network “hubs”, the activity in neuronal circuits must be first measured with a high spatiotemporal resolution. Fast multibeam two-photon calcium imaging represents the most accurate experimental system to measure the activity of large populations of neurons with single-cell resolution and will be used for the experiments. Online analysis of the network temporal dynamics will identify candidate hubs. Patch clamp recordings from these neurons while imaging will further characterize the relationship between the state of the neuron and network dynamics. Morphological reconstruction and neurochemical characterization of recorded hubs will be performed post hoc. Offline accurate mathematical analysis will reconstruct and compare the temporal dynamics of the network in control conditions and during hub stimulation. My previous studies on neuronal circuits using multi-electrode arrays and my background in Physics give me the necessary experimental and theoretical background to carry on this study and we have already obtained very encouraging preliminary results. This novel approach will be of interest to a wide audience of researchers spanning from experimental neurobiology to network theory.
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