Structured connectivity exploits NMDA non-linearities to enable flexible encoding of multiple memoranda in a PFC circuit model

Summary Prefrontal Cortex (PFC) exerts control on action selection and mediates behavioral flexibility during working memory (WM) task execution, when integration and retention of sensory information takes place. We used biophysical circuit modelling to investigate the dendritic, neuronal and circuit mechanisms that underlie these computations, aiming to causally link these three processing levels. Our simulations predict that dendritic NMDA non-linearities drive distinct activity dynamics of the same network, thus enabling adaptive coding in the absence of plasticity mechanisms. Specifically, we find that distinct assemblies of mixed-selectivity neurons emerge and fire in stable trajectories in a stimulus-dependent manner. Synaptic inputs that are spatio-temporally clustered, as provided by the structured connectivity of the PFC, facilitate these activity dynamics, thus further increasing the flexibility of the network. Our study suggests that behavioral flexibility may result from the formation of memoranda-specific assemblies in the PFC which are utilized dynamically in relation to the task at hand.