PURKINJE-CELL DENDRITIC ARBORS IN CHICK-EMBRYOS FOLLOWING CHRONIC TREATMENT WITH AN N-METHYL-D-ASPARTATE RECEPTOR ANTAGONIST

The normal development of Purkinje cell dendrites is dependent on affe rent innervation. To investigate the role of neuronal activity in Purk inje cell dendritic development, chick embryos were chronically treate d with a potent, selective, and systemically active competitive N-meth yl-D-aspartate (NMDA) receptor antagonist, NPC 12626. The NMDA recepto r was chosen as a target for pharmacological blockade because of the i mportance of the NMDA receptor in synaptic plasticity and stabilizatio n in development. Chick embryos were given daily injections of NPC 126 26 (25 to 100 mg/kg) from embryonic day 14 (E14) to E17. The initial i njections of NPC 12626 dramatically blocked embryo movements, but acti vity levels partially recovered following subsequent injections. Embry o movements were reduced by 24% at the end of the experiment, Embryos were killed on E18, and their brains processed for Golgi-Cox staining. The morphology of Golgi-stained Purkinje cells in drug-treated embryo s was similar to control embryos. Morphometric analysis showed, howeve r, that chronic treatment with NPC 12626 resulted in a 19% reduction i n Purkinje cell dendritic tree area and a 13% reduction in the number of dendritic branch points, The overall width and height of the drug-t reated dendritic trees were not significantly different from controls, suggesting that NPC 12626 reduced Purkinje cell dendritic area by int erfering with branch formation, The volume of the granule cell layer a nd the heights of the molecular and external granule cell layers was n ot reduced, suggesting that NPC 12626 treatment did not simply delay d evelopment. These results suggest that activation of the NMDA receptor may mediate the afferent-target interactions in the cerebellum that r egulate the elaboration of Purkinje cell dendrites. (C) 1995 John Wile y and Sons, Inc.