Inhibitory network predicts microstimulation-induced circuit changes in the awake mammalian cortex

Intracortical microstimulation is a powerful tool to perturb neural circuits, yet how circuit changes post-stimulation remains poorly understood. Using two-photon imaging in the awake mouse visual cortex, we tracked genetically identified neurons before, during, and after microstimulation. Even after a short 15-min microstimulation, there is pronounced suppression in excitatory neurons, accompanied by increased activity in inhibitory neurons, particularly those not recruited during microstimulation. Our findings highlight inhibition as a key player in shaping stimulation-induced circuit changes: the magnitude of plasticity in excitatory neurons is not only dependent on the level of recruitment during stimulation, but also shaped by the recruitment level of neighboring inhibitory cells, whereas the inhibitory plasticity is best explained by pre-stimulation population coupling.