THE ROLE OF THE CHOLINERGIC SYSTEM IN THE DEVELOPMENT OF THE HUMAN CEREBELLUM

High affinity(-)nicotine ([H-3]nicotine), alpha-bungarotoxin ([I-125]a lpha-bungarotoxin) and muscarinic binding ([H-3]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 autoradiogra phic study. To estimate proportions of muscarinic receptor subtypes va riable wash times and displacement with pirenzepine were employed. [H- 3]Nicotine binding and total muscarinic binding in foetuses exceeded t hat in young adults by a factor of 6 and 2 respectively in the dentate nucleus, and by a factor of 3 in white matter. [H-3]Nicotine and musc arinic binding was also higher in the foetal external granule cell lay er than in the internal granule cell layer of adult. [I-125]alpha-Bung arotoxin binding was raised in the dentate nucleus of the foetus compa red with the adult. The M(2) subtype appeared to be the predominant mu scarinic receptor in the cerebellum, however it tended to represent a lower proportion of the muscarinic binding in the foetus than the adul t. All 3 receptor types were highest in the foetal brainstem where the M(3) + M(4) muscarinic subtypes appeared to predominate. The p75 nerv e growth factor receptor, measured by immunocytochemistry, in common w ith cholinergic receptors, paralleled choline acetyltransferase activi ty which has previously been reported to be high in the cerebellum dur ing late foetal development and to fall in adulthood.