During activated states in vivo, neocortical neurons are subject to intense synaptic activity and high-amplitude membrane potential ðVmÞ fluctuations. These ‘‘high-conductance’’ states may strongly affect the integrative properties of cortical neurons. We investigated the responsiveness of cortical neurons during different states using a combination of computational models and in vitro experiments (dynamic-clamp) in the visual cortex of adult guinea pigs. Spike responses were monitored following stochastic conductance injection in both experiments and models. We found that cortical neurons can operate in a continuum between two different modes: during states with equal excitatory and inhibitory conductances, the firing is mostly correlated with an increase in excitatory conductance, which is a rather classic scenario. In contrast, during states dominated by inhibition, the firing is mostly related to a decrease in inhibitory conductances (dis-inhibition). This model predi...