Response reversal during top-down modulation in cortical circuits with multiple interneuron types

Pyramidal cells and interneurons expressing parvalbumin, somatostatin, or vasoactive intestinal peptide show cell type-specific connectivity patterns leading to a canonical microcircuit across cortex. Dissecting the dynamics of this microcircuit is essential to our understanding of the mammalian cortex. However, experiments recording from this circuit often report counterintuitive and seemingly contradictory findings. For example, the response of a V1 neural population to top-down behavioral modulation can reverse from positive to negative when the bottom-up thalamic input changes. We developed a theoretical framework to explain such response reversal, and we showed how this complex dynamics can emerge in circuits that possess two key features: the presence of multiple interneuron populations and a non-linear dependence between the input and output of the populations. Furthermore, we built a cortical circuit model and the comparison of our simulations with real data shows that our model reproduces the complex dynamics observed experimentally in mouse V1. Our explicit calculations allowed us to pinpoint the connections critical to response reversal, and to predict the existence of more types of complex dynamics that could be experimentally tested and the conditions to observe them.