Date of Award


Degree Type


Degree Name

Doctor of Philosophy


Repeated administration of low intensity electrical stimulation to the brain results in a progressive increase in the strength of epileptiform activity, culminating in a major motor seizure: the kindling effect. The present experiments investigated the effects of seizures induced early in life upon the susceptibility to kindling stimulation in the adult rat. In Experiments 1 and 2 seizures were induced with pentylenetetrazol (PTZ) or hyperthermia in male rats of different ages (1 to 21 days). Upon reaching maturity, these subjects were implanted with chronic electrodes and kindled in the basolateral amygdala. Fewer stimulations were required to produce major motor seizures in animals given a single PTZ or hyperthermia seizure at 1 day of age. No further facilitation was observed with repeated seizure episodes at 1, 3, and 5 days or 1, 5, and 9 days of age. Seizures induced at 10 or 21 days of age were without effect upon electrical kindling in the adult. Gross neuropathology or differential seizure histories could not account for the age-limited effect.;The third experiment investigated the effects of neonatal seizures upon electrical kindling of the pyriform cortex, cortical amygdaloid nucleus (ACO), and ventral hippocampus in the adult rat. As in Experiment 1, treatment with PTZ at 1-day of age facilitated ACO kindling, but was without effect on pyriform cortex or hippocampus kindling. Neither did neonatal hyperthermia seizures influence hippocampus kindling.;The restriction of a facilitatory influence of seizures to a particular developmental time period and to nuclei of the amygdaloid complex to the exclusion of other limbic sites tested is suggestive of two things: Either, (1) the amygdala, at 1, but not 10 or 21 days of age, is in a developmental state particularly sensitive to changes conducive to kindling. Other limbic structures may be sensitive at other times in development, or, (2) the amygdala represents a seizure-generating system in the limbic lobe that is differentially affected by excessive neuronal discharge coincident with seizure activity. The underlying neural systems that bring about enhanced kindling rates in the amygdala are sensitive to changes induced by seizure activity during a restricted time in development.



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