Muscarinic acetylcholine receptors are extensively involved in cortical cognition and learning-induced or experience-dependent cortical plasticity. The most abundant muscarinic receptor subtype in the cerebral cortex is the M1 receptor, but little is known about its contribution to experience-dependent plasticity of the adult auditory cortex. We have examined the role of the M1 receptor in experience-dependent plasticity of the auditory cortex in mice lacking the M1 (chrm1) gene. We show here that electrical stimulation of the basal forebrain, a major source of cortical cholinergic inputs, facilitated the auditory responses of cortical neurons in both wild types and M1 mutants. The basal forebrain stimulation alone caused change in the best frequencies of cortical neurons that were significantly greater in M1 mutants. When animals received the paired stimuli of electrical stimulation of the basal forebrain and tone, the frequency tuning of cortical neurons systematically shifted toward the frequency of the paired tone in both wild types and M1 mutants. However, the shift range in M1 mutants was much smaller than that in wild-type mice. Our data suggest that the M1 receptor is important for the experience-dependent plasticity of the auditory cortex.