Inhibitory conductance dynamics in cortical neurons during activated states.
Résumé
During activated states in vivo, neocortical neurons are subject to intense synaptic activity and highamplitude membrane potential (Vm) 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 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 prediction was tested experimentally using dynamic-clamp, and the same modes of firing were identified. We also found that the signature of spikes evoked by dis-inhibition is a transient drop of the total membrane conductance prior to the spike, which is only present in states with dominant inhibitory conductances. Such a drop should be identifiable from intracellular recordings in vivo, which would provide an important test for the presence of inhibitiondominated states. We discuss several methods to provide such an analysis. In conclusion, we show that in artificial activated states, not only inhibition can determine the conductance state of the membrane, but inhibitory inputs may also have a determinant influence on spiking. Future analyses and models should focus on evaluating the importance of inhibitory conductance dynamics from in vivo experiments.