A morphogenetic role for acetylcholine in mouse cerebral neocortex

Recently, cholinergic afferents to cerebral cortex have met renewed attention regarding the regulation of plasticity as well as cognitive processing. My laboratory has developed a mouse neonatal basal forebrain lesion paradigm that has contributed considerably to the understanding of cholinergic mechanisms in cortical development. We have shown that transient cholinergic deafferentation, beginning at birth, precipitates alterations in neuronal differentiation and synaptic connectivity that persist into maturity, and contribute to altered cognitive behavior. These data are in general agreement with studies in rats in which the cholinergic basal forebrain is lesioned very early in development but contrast with effects of later developmental lesions. Moreover, in mouse, both morphological and behavioral consequences of the lesion are sex dependent. Studies of receptors and secondary messengers that are instrumental in morphogenesis and plasticity suggest that sex dependent molecular alterations occur within days if not hours following cortical cholinergic deafferentation. (C) 2003 Elsevier Ltd. All rights reserved.