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 afferent innervation. To investigate the role of neuronal activity in Purkinje cell dendritic development, chick embryos were chronically treated with a potent, selective, and systemically active competitive N-methyl-D-aspartate (NMDA) receptor antagonist, NPC 12626. The NMDA receptor was chosen as a target for pharmacological blockade because of the importance of the NMDA receptor in synaptic plasticity and stabilization in development. Chick embryos were given daily injections of NPC 12626 (25 to 100 mg/kg) from embryonic day 14 (E14) to E17. The initial injections of NPC 12626 dramatically blocked embryo movements, but activity levels partially recovered following subsequent injections. Embryo 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 embryos was similar to control embryos. Morphometric analysis showed, however, that chronic treatment with NPC 12626 resulted in a 19% reduction in Purkinje cell dendritic tree area and a 13% reduction in the number of dendritic branch points. The overall width and height of the drug-treated dendritic trees were not significantly different from controls, suggesting that NPC 12626 reduced Purkinje cell dendritic area by interfering with branch formation. The volume of the granule cell layer and the heights of the molecular and external granule cell layers was not reduced, suggesting that NPC 12626 treatment did not simply delay development. These results suggest that activation of the NMDA receptor may mediate the afferent-target interactions in the cerebellum that regulate the elaboration of Purkinje cell dendrites.
Vogel
M W
MW
Maryland Psychiatric Research Center, Baltimore 21228, USA.
Prittie
J
J
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D002642:Chick Embryo; D003712:Dendrites / Q000187:drug effects* / Q000648:ultrastructure; D009068:Movement / Q000187:drug effects; D011689:Purkinje Cells / Q000187:drug effects* / Q000648:ultrastructure; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013997:Time Factors
D000596:Amino Acids; D016194:Receptors, N-Methyl-D-Aspartate; C060212:NPC 12626