The nicotinic cholinergic system influences cognition, anxiety, locomotion, and addiction by acting upon nicotinic acetylcholine receptors (nAChRs). To date, there are 12 known neuronal mammalian nAChR subunits leading to a rich pharmacological diversity that is difficult to attribute to specific subunits. We generated alpha7-beta2 nAChR double mutant mice by breeding to investigate the effect of a minimal number of nAChRs in the CNS. These mice have been used to determine the role these receptor subunits play in a variety of behaviors. A battery of behavioral tests was used to determine the effect of the mutation in anxiety, locomotor activity, startle response, pre-pulse inhibition, motor coordination and learning and memory. Mice lacking both the alpha7 and the beta2 nAChR subunits displayed impaired learning and memory performance in a passive avoidance test and showed enhanced motor performance on the rotarod.