Despite impressive advances in almost every field of neuroscience, our insights into brain function remain largely confined to its building blocks at the microscopic level, and to phenomenological descriptions at the macroscopic level. Understanding how complex mental functions originate from electrical and chemical processes in brain cells requires a comprehensive and integrated multi-level analysis focused on neuronal assemblies and microcircuits, where myriads of intricately connected neurons with different properties act together. We shall use the coordinator’s recent discovery of entorhinal grid cells – a key cell type in the network for spatial representation and navigation – as a model for neuronal computation in non-sensory cortical microcircuits. The crystal-like structure of the firing fields of grid cells provides an entirely new route to access the neuronal interactions responsible for pattern formation in the brain. Using a forceful combination of computational modelling and novel electrophysiological, optical and molecular research tools never applied for circuit analyses in the brain before, we shall establish the mechanisms by which microcircuits in the hippocampus and entorhinal cortex encode, maintain and update representations of location as animals move from one place to another. Insights into the underlying computations have considerable translation potential. Understanding the algorithms for spatial navigation may change the way we manage a number of diseases, including Alzheimer’s disease, which commonly begins in the entorhinal cortex and has topographical disorientation as one of its most reliable symptoms, and it may provide European industry with radically innovative concepts for the design of artificial navigating agents.
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