Summary Cortical dynamics underlie many cognitive processes and emerge from complex multi-scale interactions, which can be studied in large-scale, biophysically detailed models. We present a model comprising eight somatosensory cortex subregions, 4.2 million morpho-logical and electrically-detailed neurons, and 13.2 billion local and long-range synapses. In silico tools enabled reproduction and extension of complex laboratory experiments under a single parameterization, providing strong validation. We reproduced millisecond-precise stimulus-responses, stimulus-encoding under targeted optogenetic activation, and selective propagation of stimulus-evoked activity to downstream areas. The model’s di-rect correspondence with biology generated predictions about how multiscale organisation shapes activity. We predict that structural and functional recurrency increases towards deeper layers and that stronger innervation by long-range connectivity increases local correlated activity. The model also predicts the role of inhibitory interneuron types in stimulus encoding, and of different layers in driving layer 2/3 stimulus responses. Simu-slation tools and a large subvolume of the model are made available.

Modeling and Simulation of Neocortical Micro- and Mesocircuitry. Part II: Physiology and Experimentation