Author SummaryThe neocortex of the mammalian brain contains many more excitatory neurons than inhibitory neurons, yet inhibitory neurons are essential components of neocortical circuitry. Inhibitory neurons form dense and intricate connections with excitatory neurons, which are mainly pyramidal cells. One prominent pathway formed between pyramidal cells and inhibitory Martinotti cells is frequency-dependent disynaptic inhibition (FDDI), which mediates a strong inhibitory signal in the microcircuitry of the neocortex. Here, we reveal deeper insight into how FDDI is mediated and recruited within the circuit, showing that short simultaneous bursts in four pyramidal cells are sufficient to exert FDDI in all neighboring pyramidal cells within the dimensions of a cortical column. As few as three synchronous action potentials in three pyramidal cells can trigger FDDI. This powerful inhibition is mediated by only a few inhibitory neurons yet correlates membrane potential fluctuations, leading to synchronous spiking between pyramidal cells that simultaneously receive FDDI. The inhibitory signals are independent and electrically isolated from excitation mediated by neighboring PCs via basal dendrites. We propose FDDI as an important pathway that is readily activated by brief bursts of action potentials and correlates neocortical network activity.