Abstract How does cellular organization shape the spatio-temporal patterns of activity in the cortex while processing sensory information? After measuring the propagation of activity in the mouse primary somatosensory cortex (S1) in response to single whisker deflections with Voltage Sensitive Dye (VSD) imaging, we developed a two dimensional mean field model of S1. We observed that, for strong enough excitatory cortical interactions, whisker deflections generate a propagating wave in S1. We developed an inversion method that reconstructs model parameters from VSD data, revealing that a spatially heterogeneous organization of synaptic strengths between pyramidal neurons in S1 is likely to be responsible for the anisotropic spatio-temporal patterns of activity measured experimentally. Finally, we report that two consecutive stimuli activating different spatial locations in S1 generate two waves which collide sub-linearly. In the model, such sub-linear interaction is explained by a lower sensitivity to external perturbations of neural networks during activated states.