Cholinergic modulation of neuronal excitability and recurrent excitation‐inhibition in prefrontal cortex circuits: implications for gamma oscillations

•  Previous studies indicate that cholinergic neuromodulation is required for cognitive processes and for gamma oscillatory activity in neocortical networks in vivo. The cholinergic agonist carbachol (CCh) induces gamma oscillations in vitro, via mechanisms that may be shared with those mediating in vivo gamma oscillations. •  Here, we studied the effects of CCh on cortical circuit components thought to be critical for gamma oscillations, and found that CCh stimulated firing of pyramidal cells (PCs) and increased excitatory synaptic input onto fast‐spiking interneurons (FSNs). •  CCh also modulated synaptic transmission between FSNs and PCs, decreasing synaptic depression during repetitive presynaptic firing, while simultaneously reducing the unitary synaptic currents. •  CCh increased the probability of neuron firing per oscillation cycle when PCs and FSNs fired in response to oscillatory input at gamma frequency. •  Combined, these effects of CCh may help explain the contribution of cholinergic modulation to gamma oscillations.