Cortical and nigral deafferentation and striatal cholinergic markers in the rat dorsal striatum: different effects on the expression of mRNAs encoding choline acetyltransferase and muscarinic m1 and m4 receptors

The regulation of the striatal m1 and m4 muscarinic receptor mRNA as well a s the choline acetyltransferase (ChAT) mRNA expression by nigral dopaminerg ic and cortical glutamatergic afferent fibres was investigated using quanti tative in situ hybridization histochemistry. The effects induced by a unila teral lesion of the medial forebrain bundle and a bilateral lesion of the s ensorimotor (SM) cortex were analysed in the dorsal striatum 3 weeks after the lesions. Dopaminergic denervation of the striatum resulted in a marked decrease in the levels of m4 mRNA throughout the striatum, while the levels of muscarinic m1 mRNA and ChAT mRNA in cholinergic neurons were unaffected by the lesion. In contrast, following bilateral cortical ablation, the lev els of the muscarinic m1 mRNA were significantly increased in the striatal projection area of the SM cortex, whereas the expression of m4 mRNA remaine d unchanged. single cholinergic cell analysis by computer-assisted grain co unting revealed a decreased labelling for ChAT mRNA per neuron following co rtical ablation. However, in contrast to the topographical m1 mRNA changes, the decreased ChAT mRNA expression was evenly distributed within the stria tum, suggesting an indirect cortical control upon striatal cholinergic inte rneurons. Altogether, these data suggest that dopaminergic nigral and gluta matergic cortical afferents modulate differentially cholinergic markers, at the pre- and post-synaptic levels. Beside the fact that nigral and cortica l inputs exert an opposite control on cholinergic neurotransmission, our st udy further shows that this control involved different muscarinic receptor subtypes: the m4 and m1 receptors, respectively.