The role of the cholinergic system in the development of the human cerebellum

Abstract

High affinity (−)nicotine ([ 3H]nicotine), α-bungarotoxin ([ 1251]α-bungarotoxin) and muscarinic binding ([ 3H] N-methyl scopolamine) in the human cerebellum were compared between the foetal period (23–39 weeks gestation) and young adulthood (14–34 years) in an autoradiographic study. To estimate proportions of muscarinic receptor subtypes variable wash times and displacement with pirenzepine were employed. [ 3H]Nicotine binding and total muscarinic binding in foetuses exceeded that in young adults by a factor of 6 and 2 respectively in the dentate nucleus, and by a factor of 3 in white matter. [ 3H]Nicotine and muscarinic binding was also higher in the foetal external granule cell layer than in the internal granule cell layer of adult. [ 125I]α-Bungarotoxin binding was raised in the dentate nucleus of the foetus compared with the adult. The M 2 subtype appeared to be the predominant muscarinic receptor in the cerebellum, however it tended to represent a lower proportion of the muscarinic binding in the foetus than the adult. All 3 receptor types were highest in the foetal brainstem where the M 3 + M 4 muscarinic subtypes appeared to predominate. The p75 nerve growth factor receptor, measured by immunocytochemistry, in common with cholinergic receptors, paralleled choline acetyltransferase activity which has previously been reported to be high in the cerebellum during late foetal development and to fall in adulthood.