Abstracts

Neuronal activity plays a crucial role in the proper development and maturation of the immature brain. The present project investigates the consequences of activity blockade during critical periods of brain development., Postnatal day 10 (P10) rats were implanted with a subcutaneous Alzet pump (2 or 4 weeks capacity) filled with 10 [micro]M tetrodotoxin (TTX). The infusion cannula was implanted either in the cortex or dorsal hippocampus. At the end of the infusion period (at P25 or P39) the pump was removed and animals were implanted with a series of cortical and/or hippocampal silver EEG electrodes. On the following day EEG/video recordings of 2 [ndash] 4 hours duration were initiated. Monitoring was repeated at approximately daily intervals for at least 1 week. All surgical procedures and animal care have been approved by Baylor College of Medicine., To date 35 TTX treated (17 cortical -1 two weeks and 16 four weeks infusion and 18 hippocampal - 6 two weeks and 12 four weeks) and 5 vehicle infused (hippocampal - 4 weeks) animals have been implanted and monitored. All TTX treated animals exhibited high voltage multifocal interictal spiking. A subset of 4 weeks infused animals from each infusion area (3 of 16 cortical and 3 of 12 hippocampal) exhibited sporadic EEG complexes consisting of a generalized slow wave transient, a generalized voltage attenuation (2-4 seconds) or a burst of fast activity (2-4 seconds) .These complexes could occur alone or in various combinations, the most common being a high voltage slow wave complex followed by a generalized voltage attenuation with superimposed fast activity. These complexes could occur in isolation or in clusters and typically occurred on arousal from sleep. These EEG complexes were typically associated behaviorally with a brief tonic spasm, which could be preceded by a body jerk. Some of these animals also exhibited a very high voltage background EEG pattern associated with multifocal sharp wave discharges that resembled the hypsarrhythmic pattern observed in human children with infantile spasms. No seizure activity was observed in 2 week infused animals or in any of the vehicle infused animals., The results suggest that prolonged blockade of neuronal activity during critical periods in early life can induce seizures. Some of these animals exhibited EEG and behavioral phenotypes that are very similar to those found in human cases of infantile spasms., (Supported by NIH (NINDS) Grants: NS 18309 and NS37171.)