Delineating and testing a microcircuit model of parahippocampal phase precession

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Throughout the hippocampal formation, the firing activity of place or grid cells and the EEG theta rhythm (~8Hz) are related: When an animal enters a cell´s firing field, the first spikes arrive at a late phase of the theta oscillation. As the animal traverses the field, the spikes in subsequent cycles of the theta oscillation arrive at earlier and earlier phases. Spikes "precess" throughout the place field. Phase precession is one of the most investigated topics in systems neuroscience and might be instrumental in matching the time scale of behavioral learning, which occurs in the range of seconds or more, to the time scales of synaptic plasticity, which are often in the range of milliseconds. Previous research on phase precession resulted in a rich description of the temporal discharge phenomenology of neurons and in numerous models of phase precession. Still the mechanism(s) underlying phase precession are unknown. We will try to solve this problem by analyzing layer 3 of the entorhinal cortex, where neurons show prominent phase precession. Previous attempts to explain phase precession suffered from four intertwined problems: (1) phase precession models are typically underconstrained, (2) most studies do not formulate precise microcircuit models, (3) models are therefore not strongly predictive, (4) models are typically not tested, i.e. they are experimentally inconsequential. The unique composition and the complementary expertise of our research consortium will allow us to overcome these problems: (i) Connectivity analysis and high-resolution recordings will delineate entorhinal microcircuits with unprecedented precision. (ii) These data will be funneled into a strongly predictive microcircuit model. (iii) Accordingly, this model can be tested in vitro and in vivo. Our approach will enable us to selectively interfere with phase precession and test its role in spatial memory formation.