Working memory signal in prefrontal cortex: local network interactions, layer dependence and neuropharmacology (360G-Wellcome-099757_Z_12_A)

The project aims to elucidate how subdomains within the prefrontal cortex inteinteract during execution of a working memory task, and how these interactions are gated by dopaminergic and cholinergic neuromodulation. We will map the representation of saccade space in the dorsolateral prefrontal cortex (DLPFC) and map the (local) functional connectivity between domains therein by means of fMRI. We will then target functionally connected locations/columns and rcuirecord across cortical layers (laminar electrode recordings) while an animal model performs a working memory task (memory guided delayed saccade task). These recordings will be performed without and with simultaneous local infusion of selective dopaminergic and cholinergic receptor antagonists and agonists. The key goals are: (1) To understand to what extent functional connectivity (measured by means of resting state fMRI and task related fMRI) within the prefrontal cortex maps onto similarity of function (measured by means of electrophysiological recordings). (2) To understand the flow of information within and between canonical microcircuits in the DLPFC and how this enables the maintenance of working memory signals. Specifically, we aim to understand how the flow of information is gated in andbetween different cortical layers and to understand the neuropharmacology thatgoverns gating and interactions between different local networks.