Regional differences in the critical period neurodevelopment in the mouse: implications for neonatal seizures.

The voltage-sensitive calcium channel probe 125I-omega-GVIA conotoxin has been shown to be a developmental marker in whole brain preparations of Swiss Webster mice. The present study looks more carefully at regional dissections of the mouse brain (cerebrum, cerebellum, and brain stem) at postnatal day 8 and postnatal day 16. 125I-omega-GVIA conotoxin binding, thought to be presynaptic, showed a dramatic increase between postnatal days 8 and 16 in the cerebral cortex, a decrease in the cerebellum, and no change in the brain stem. The dramatic cerebral cortex increases indicated by these binding data correspond to a critical period between postnatal day 11 and postnatal day 14 in Swiss Webster mice; during this critical period, dendrites exhibit rapid outgrowth, sensory modalities come on line, electroencephalographic patterns mature, and the cortex reaches adult proportions. This period parallels a similar initiation of electrical maturation in the 28- to 32-week neonatal human brain. We conclude from these data that the unusual clinical presentation of neonatal seizures is not just the result of immature myelin formation. It includes incomplete synapse formation linking the cortex to the brain stem.

Voltage sensitive calcium channels mark a critical period in mouse neurodevelopment.

Voltage sensitive calcium channel (VSCC) probes 125I-omega-GVIA Conotoxin (omega-GVIA), (+)-[5-methyl-3H]-PN200-110 (3H-PN200), and 3H-Nimodipine were bound to developing Swiss Webster mouse whole brain from postnatal days 3 to 24. 125I-omega-GVIA binding, thought to be presynaptic, showed a 50% increase between days 11 and 14. 3H-dihydropyridine binding, thought to be postsynaptic, showed spike patterns when measured developmentally. 3H-PN200 binding showed a > 150% increase between days 11 and 15. 3H-Nimodipine binding showed a > 100% increase between days 11 and 14. Depolarization-induced 45Ca 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.