Intra- and inter-layer entorhinal circuit mechanisms for estimating location

The well characterised spatial firing of neurons in the medial entorhinal cortex (MEC) make this structure an excellent model for investigation of cognitive circuitry. However, progress in moving from descriptions of its activity to an understanding of its circuit computations is hindered by functional specialisation of cell types with and between its layers, limited availability of tools for selectively manipulating key cell types and difficulty in dissociating roles of spatial from self-motion signals. We propose to address these challenges by combining new behavioural paradigms with precise molecular genetic manipulation of MEC circuitry, and electrophysiological recordings of neuronal activity. We aim to delineate synaptic interactions of key molecularly defined neuronal populations in layers 2 and 5b, and investigate contributions of these neuronal populations to network oscillations, spatial firing and behaviour. In doing so we will distinguish predictions of distinct models for spatial computation that imply differing roles for intra- and inter-layer interactions. Our strategic approach, focussed on two key cell populations, will generate experimental and theoretical frameworks that are extendable to additional cell types in the MEC and other cortices, and that will be a foundation for future mechanistic investigation of molecular underpinnings of spatial cognition.