Synaptic inhibition in the neocortex: Orchestration and computation through canonical circuits and variations on the theme.

The neocortex plays a crucial role in all basic and abstract cognitive functions. Conscious mental processes are achieved through a correct flow of information within and across neocortical networks, whose particular activity state results from a tight balance between excitation and inhibition. The proper equilibrium between these indissoluble forces is operated with multiscale organization: along the dendro-somatic axis of single neurons and at the network level. Fast synaptic inhibition is assured by a multitude of inhibitory interneurons. During cortical activities, these cells operate a finely tuned division of labor that is epitomized by their detailed connectivity scheme. Recent results combining the use of mouse genetics, cutting-edge optical and neurophysiological approaches have highlighted the role of fast synaptic inhibition in driving cognition-related activity through a canonical cortical circuit, involving several major interneuron subtypes and principal neurons. Here we detail the organization of this cortical blueprint and we highlight the crucial role played by different neuron types in fundamental cortical computations. In addition, we argue that this canonical circuit is prone to many variations on the theme, depending on the resolution of the classification of neuronal types, and the cortical area investigated. Finally, we discuss how specific alterations of distinct inhibitory circuits can underlie several devastating brain diseases.