Disruption of nicotinic acetylcholine receptor (nAChR) signalling in the prefrontal cortex has been suggested to underlie cognitive deficits in schizophrenia. In this study, mice expressing a variant of human nAChR subunit α5 implicated in schizophrenia showed impaired sociability and sensorimotor gating. Two-photon calcium imaging revealed that these mice have lower pyramidal neuron activity in layers 2/3 of the prelimbic cortex, and this activity was normalized by chronic nicotine infusion, suggesting nicotine could have potential in treating cognitive symptoms of schizophrenia.