Cortical glutamatergic projection neuron types contribute to distinct functional subnetworks

The cellular basis of cerebral cortex functional architecture remains not well understood. A major challenge is to monitor and decipher neural network dynamics across broad cortical areas yet with projection-neuron-type resolution in real time during behavior. Combining genetic targeting and wide-field imaging, we monitored activity dynamics of subcortical-projecting (PT^Fezf2) and intratelencephalic-projecting (IT^PlxnD1) types across dorsal cortex of mice during different brain states and behaviors. IT^PlxnD1 and PT^Fezf2 neurons showed distinct activation patterns during wakeful resting, during spontaneous movements and upon sensory stimulation. Distinct IT^PlxnD1 and PT^Fezf2 subnetworks were dynamically tuned to different sensorimotor components of a naturalistic feeding behavior, and optogenetic inhibition of ITs^PlxnD1 and PTs^Fezf2 in subnetwork nodes disrupted distinct components of this behavior. Lastly, IT^PlxnD1 and PT^Fezf2 projection patterns are consistent with their subnetwork activation patterns. Our results show that, in addition to the concept of columnar organization, dynamic areal and projection-neuron-type specific subnetworks are a key feature of cortical functional architecture linking microcircuit components with global brain networks.