Decreased input-specific plasticity of the auditory cortex in mice lacking M1 muscarinic acetylcholine receptors

Muscarinic acetylcholine receptors are extensively involvedin cortical cognition and learning-induced or experience-dependentcortical plasticity. The most abundant muscarinic receptor subtypein the cerebral cortex is the M₁ receptor, but little is knownabout its contribution to experience-dependent plasticity ofthe adult auditory cortex. We have examined the role of theM₁ receptor in experience-dependent plasticity of the auditorycortex in mice lacking the M₁ (chrm1) gene. We show here thatelectrical stimulation of the basal forebrain, a major sourceof cortical cholinergic inputs, facilitated the auditory responsesof cortical neurons in both wild types and M₁ mutants. The basalforebrain stimulation alone caused change in the best frequenciesof cortical neurons that were significantly greater in M₁ mutants.When animals received the paired stimuli of electrical stimulationof the basal forebrain and tone, the frequency tuning of corticalneurons systematically shifted toward the frequency of the pairedtone in both wild types and M₁ mutants. However, the shift rangein M₁ mutants was much smaller than that in wild-type mice.Our data suggest that the M₁ receptor is important for the experience-dependentplasticity of the auditory cortex.