Disrupted tonotopy of the auditory cortex in mice lacking M1 muscarinic acetylcholine receptor

Sensory cortices have multiple and distinct functional maps that systematically represent environmental information. Development of these maps is precisely controlled by a number of intrinsic and extrinsic factors. Cortical cholinergic regulation is a crucial factor for normal cortical morphogenesis. In this study, we test the role of the M-1 muscarinic acetylcholine receptor, the main muscarinic receptor subtype in the neocortex in the development of tonotopic maps in the auditory cortex. Mice lacking M-1 receptors have normal hearing sensitivity but exhibit disrupted tonotopic organization and frequency tuning in the auditory cortex. In contrast, tonotopic organization and frequency tuning remain normal in the auditory midbrain. In addition, cortical layer IV neurons of M-1 mutants exhibit significantly shorter or sparser dendrites compared to neurons of wildtype mice. In summary, our data suggest that the M-1 receptor appears to be critical for the refinement or normal maturation of cortical tonotopy that is guided by thalamocortical inputs during early development. (c) 2004 Elsevier B.V. All rights reserved.