Abstract
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 (M1-5). 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.
Highlights
Sensory cortices begin to form and make intracortical and subcortical connections early in the developmental regime, and the auditory cortex is no exception
During early development several key neuronal projections make connections in the cortex, and here we focus on two: one consists of glutamatergic axons from thalamic relay cells, through which the cortex receives the majority of its environmental input [4], and the other comprises cholinergic axons, primarily from the basal forebrain
In vitro experiments have demonstrated that M1 activation can signal through PKCε, resulting in robust outgrowth of neurites from pyramidal cells [26]. These in vitro studies suggest an interpretation that M1 contributes to neurite outgrowth in vivo as well; the length of dendrites of layer 4 multipolar granular cells in the auditory cortex was significantly shorter in M1 knockout mice than in wildtype controls [28]
Summary
Sensory cortices begin to form and make intracortical and subcortical connections early in the developmental regime, and the auditory cortex is no exception. In vitro experiments have demonstrated that M1 activation can signal through PKCε, resulting in robust outgrowth of neurites from pyramidal cells [26] These in vitro studies suggest an interpretation that M1 contributes to neurite outgrowth in vivo as well; the length of dendrites of layer 4 multipolar granular cells in the auditory cortex was significantly shorter in M1 knockout mice than in wildtype controls [28]. It is possible that M1 plays some previously unexplored role in layer 4 of the auditory cortex; the shortening of dendrites in the absence of M1signalling in vivo may be a more general phenomenon than has been documented so far This observation may be indicative of an alteration in either the thalamic innervation of the cortex, or the formation of synapses from thalamocortical afferents onto cortical neurons (usually in layer 4), in mice lacking M1 receptors [28]. As our basic understanding of the roles of these receptors increases, it is likely that our insight into the associated pathologies will increase
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