Electroanatomy of hippocampal networks: Topographic distribution of co-active cells and its plasticity

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Local neuronal networks express highly coordinated spatiotemporal activity patterns. The participating neurons form functional ensembles which are believed to constitute elementary representations of percepts, actions, or memories. In line with their different cognitive-behavioral functions, characteristic properties of such ensembles (number of neurons, sparsity of firing, overlap between different representations, spatial arrangement) are likely to differ between different networks. However, there is very little quantitative, comparative data on these parameters. We want to provide such a comparison in a prominent model system for spatial memory formation, the hippocampal-entorhinal network. This structure contains several interconnected local networks with different connectivity and behavioral significance. Recent work has revealed specific operations performed by the sub-networks, e.g. the decorrelation of incoming information in the dentate gyrus (pattern separation) and the attractor dynamics of CA3 (pattern completion). The basic circuitry, cell types, short- and long-range connections, and patterns of collective network behavior have been well studied. Little is known, however, about the size, overlap and spatial organization of ensembles in each hippocampal-entorhinal sub-network. The heterogeneity of local, interconnected networks, the laminar organization of the brain area, and the good knowledge of cellular and network properties make this system ideal for a comparative study of the ensembles. Using a high-resolution electrode microarray as a unique new tool, we will simultaneously record from large numbers (hundreds to thousands) of cells. This will allow studying the geometry of ensembles throughout the hippocampal-entorhinal system, and to compare the location, extent, separation and topology of ensembles. Propagating activity patterns can be followed through different local networks, revealing whether topological orders are maintained or systematically changed. Complementary approaches at the cellular level will unravel distinct cell-to-network coupling mechanisms, and experiments at the behavioral level will validate findings from in vitro recordings in native networks. Specifically, we will (1) map the spatial organization of ensembles within each network; (2) search for topologically organized input-output relationships between different local networks; (3) correlate the activity of single cells with network-level activity patterns; (4) assess the effect of neuromodulators on the respective patterns; (5) test the findings from (i)-(iv) in recordings from behaving mice in vivo.Together, we aim at a comprehensive network-level comparison of different hippocampal-entorhinal networks, resulting in a functional 'electroanatomy' of this important brain region.