Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for reconstructing and simulating neocortical microcircuitry. In one aspect, a method includes providing a model of neural tissue, the model including different types of neural cells and dynamic synaptic interconnections between the neural cells, changing a parameter in the model; and identifying a change in a computational state of the model of the neural tissue responsive to the change in the parameter. The change in the parameter can, e.g., change behavior of neural cells of at least one type, change interconnectivity between neural cells, or target a location within a volume in the model that interacts with multiple types of neural cells.