Scanning mutagenesis of the I-II loop of the Cav2.2 calcium channel identifies residues Arginine 376 and Valine 416 as molecular determinants of voltage dependent G protein inhibition

The sensory cortex is subject to continuous remodelling during early development and throughout adulthood. This process is important for establishing normal brain function and is dependent on cholinergic modulation via muscarinic receptors. Five muscarinic receptor genes encode five unique receptor subtypes (M_1-5). The distributions and functions of each subtype vary in central and peripheral systems. In the brain, the M₁ receptor is most abundant in the cerebral cortex, where its immunoreactivity peaks transiently during early development. This likely signifies the importance of M₁ receptor in the development and maintenance of normal cortical function. Several lines of study have outlined the roles of M₁ receptors in the development and plasticity of the auditory cortex. For example, M₁-knockout reduces experience-dependent plasticity and disrupts tonotopic mapping in the adult mouse auditory cortex. Further evidence demonstrates a role for M₁ in neurite outgrowth and hence determining the structure of cortical neurons. The disruption of tonotopic maps in M₁-knockout mice may be linked to alterations in thalamocortical connectivity, because the targets of thalamocortical afferents (layer IV cortical neurons) appear less mature in M₁ knockouts. Herein we review the literature to date concerning M₁ receptors in the auditory cortex and consider some future directions that will contribute to our understanding.