Voltage-sensitive dye (VSD) imaging produces an unprecedented real-time and high-resolution mesoscopic signal to measure the cortical population activity. We have previously shown that the neuronal compartments contributions to the signal are dynamic and stimulus-dependent (Chemla S, Chavane F. Neuroimage 53: 420 – 438, 2010). Moreover, the VSD signal can also be strongly affected by the network state, such as in anesthetized vs. awake preparations. Here, we investigated the impact of the network state, through GABA A receptors modulation, on the VSD signal using a computational approach. We therefore systematically measured the effect of the GABA A-mediated inhibitory post-synaptic potentials (IPSPs) decay time constant (G) on our modeled VSD response to an input stimulus of increasing strength. Our simulations suggest that G strongly modulates the dynamics of the VSD signal, affecting the amplitude, input response function, and the transient balance of excitation and inhibition. We confirmed these predictions experimentally on awake and anesthetized monkeys, comparing VSD responses to drifting gratings stimuli of various contrasts. Lastly, one in vitro study has suggested that GABA