VOLTAGE SENSITIVE CALCIUM CHANNELS MARK A CRITICAL PERIOD IN MOUSE NEURODEVELOPMENT

Voltage sensitive calcium channel (VSCC) probes I-125-omega-GVIA Conotoxin (omega-GVIA), (+)-[5-methyl-H-3]-PN200-110 (H-3-PN200), and H-3-Nimodipine were bound to developing Swiss Webster mouse whole brain from postnatal days 3 to 24. I-125-omega-GVIA binding, thought to be presynaptic, showed a 50% increase between days 11 and 14. H-3-dihydropyridine binding, thought to be postsynaptic, showed spike patterns when measured developmentally. H-3-PN200 binding showed a > 150% increase between days 11 and 15. H-3-Nimodipine binding showed a > 100% increase between days 11 and 14. Depolarization-induced Ca-45 fluxes also increased between days 8 and 16 by > 500%. The dramatic increases indicated by these binding data correspond to a critical period described by Himwich (Int. Rev. Neurobiol. 4, 117, 1962) between postnatal days 11 and 14 in Swiss Webster mice; during this critical period, dendrites exhibit rapid outgrowth, sensory modalities come on line, EEG patterns mature, and the cortex reaches adult proportions. We conclude from these data that the increase in VSCC activity parallels a critical period in the development of the central nervous system in Swiss Webster mice.